Pyrazole derivative, intermediate therefor, processes for producing these, and herbicide containing these as active ingredient

ABSTRACT

The present invention provides a pyrazole derivative of the general formula (1), 
                         
which has an excellent efficacy as an active component for a herbicide, an intermediate for the production thereof, processes for the production thereof, and a herbicide containing the derivative as an active ingredient.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a National Phase Entry of co-pending InternationalApplication No. PCT/JP02/01411, filed Feb. 19, 2002 which designated theU.S. and which claims the benefit of Japanese Application No.2001-43199, filed Feb. 20, 2001.

TECHNICAL FIELD

The present invention relates to a novel pyrazole derivative, anintermediate thereof, processes for the preparation thereof and aherbicide containing any one of them as an active ingredient.

TECHNICAL BACKGROUND

Conventionally, there are known a number of pyrazole derivatives havingpesticidal activity such as herbicidal activity or insecticidalactivity. However, nothing has been reported on any pyrazole derivativehaving a substituted oxy group at the 3-position of a pyrazole ring anda substituted carbamoyl group or a substituted thiocarbamoyl group on anitrogen atom at the 1-position as shown in the following generalformula (1) in the present invention, nor is there any report onbiological activities thereof. As pyrazole derivatives structurallysimilar to the pyrazole derivative (1) of the present invention, thereare known pyrazole derivatives described in WO97/24332 (EP876351,JP2000/502686, U.S. Pat. No. 6,075,149) and EP256667 (JP63/044571, U.S.Pat. No. 5,374,644). However, these pyrazole derivatives are completelydifferent from the pyrazole derivative (1) of the present invention inthat they have an alkyl group on a nitrogen atom of their pyrazole ring.Further, it is described that the pyrazole derivatives described in theabove WO97/24332 and EP256667 have pesticidal activity against fungi andharmful insects, but these Publications describe nothing concerning anyother biological activity.

DISCLOSURE OF THE INVENTION

The present invention provides a novel pyrazole derivative havingexcellent herbicidal activity and high selectivity to crops, anintermediate thereof and processes for the preparation thereof, andfurther provides a herbicide containing the derivative as an activeingredient.

The present inventors have made diligent studies for herbicides havingexcellent herbicidal activity and crop selectivity. As a result, it hasbeen found that the pyrazole derivative of the following general formula(1) in the present invention exhibits excellent herbicidal activity at alow dosage without causing phytotoxicity, and a simple process for thepreparation thereof has been also found. The present invention has beenaccordingly completed.

That is, the present invention is directed to a pyrazole derivative ofthe general formula (1),

-   -   wherein R¹ is a hydrogen atom, an optionally substituted alkyl        group having 1 to 6 carbon atoms, an optionally substituted        cycloalkyl group having 3 to 8 carbon atoms, an alkyloxycarbonyl        group having 1 to 6 carbon atoms or an optionally substituted        phenyl group, R² is a hydrogen atom, a halogen atom or an        optionally substituted alkyl group having 1 to 6 carbon atoms,        R³ is a hydrogen atom, an optionally substituted alkyl group        having 1 to 12 carbon atoms, an optionally substituted        cycloalkyl group having 3 to 8 carbon atoms, an optionally        substituted aralkyl group having 7 to 11 carbon atoms, an        optionally substituted alkenyl group having 3 to 6 carbon atoms,        an optionally substituted alkynyl group having 3 to 6 carbon        atoms, an optionally substituted phenyl group, an optionally        substituted alkyloxy group having 1 to 6 carbon atoms, an        optionally substituted cycloalkyloxy group having 3 to 8 carbon        atoms, an optionally substituted aralkyloxy group having 7 to 11        carbon atoms, an optionally substituted alkenyloxy group having        3 to 6 carbon atoms, an optionally substituted alkynyloxy group        having 3 to 6 carbon atoms or an optionally substituted        phenyloxy group, R⁴ is a hydrogen atom, an optionally        substituted alkyl group having 1 to 12 carbon atoms, an        optionally substituted cycloalkyl group having 3 to 8 carbon        atoms, an optionally substituted aralkyl group having 7 to 11        carbon atoms, an optionally substituted alkenyl group having 3        to 6 carbon atoms, an optionally substituted alkynyl group        having 3 to 6 carbon atoms or an optionally substituted phenyl        group, or, R³ and R⁴ may form a heterocyclic ring together with        a nitrogen atom to which they bond, R⁵ is an optionally        substituted phenyl group or an optionally substituted pyridyl        group, and Y is an oxygen atom or a sulfur atom.

Further, the present invention is also directed to a pyrazole derivativeof the general formula (2),

wherein R¹, R² and R⁵ are as defined above.

Further, the present invention is directed to a process for thepreparation of a pyrazole derivative of the general formula (2),

wherein R¹, R² and R⁵ are as defined above,

which comprises reacting a 3-hydroxypyrazole derivative of the generalformula (3),

wherein R¹ and R² are as defined above, and a compound of the generalformula (4),R⁵—Z  (4)

wherein R⁵ is as defined above and Z is a leaving group,

in the presence of a base.

Further, the present invention is directed to a process for thepreparation of a pyrazole derivative of the general formula (2b),

wherein R¹ is as defined above, R^(5a) is a hydrogen atom, an optionallysubstituted phenyl group or an optionally substituted pyridyl group andR^(2a) is a halogen atom,

which comprises halogenating a pyrazole derivative of the generalformula (2a),

wherein R¹ and R^(5a) are as defined above.

Further, the present invention is directed to a process for thepreparation of a pyrazole derivative of the general formula (1a) in thepresent invention,

wherein R¹, R², R^(5a) and Y are as defined above, and R^(3a) is anoptionally substituted alkyl group having 1 to 12 carbon atoms, anoptionally substituted cycloalkyl group having 3 to 8 carbon atoms, anoptionally substituted aralkyl group having 7 to 11 carbon atoms, anoptionally substituted alkenyl group having 3 to 6 carbon atoms, anoptionally substituted alkynyl group having 3 to 6 carbon atoms, anoptionally substituted phenyl group, an optionally substituted alkyloxygroup having 1 to 6 carbon atoms, an optionally substitutedcycloalkyloxy group having 3 to 8 carbon atoms, an optionallysubstituted aralkyloxy group having 7 to 11 carbon atoms, an optionallysubstituted alkenyloxy group having 3 to 6 carbon atoms, an optionallysubstituted alkynyloxy group having 3 to 6 carbon atoms or an optionallysubstituted phenyloxy group,

which comprises reacting a pyrazole derivative of the general formula(2c),

wherein R¹, R² and R^(5a) are as defined above,

and isocyanates or isothiocyanates of the general formula (5),R^(3a)—NCY  (5)

wherein R^(3a) and Y are as defined above, optionally in the presence ofa base.

Further, the present invention is directed to a process for thepreparation of a pyrazole derivative of the general formula (1b),

wherein R¹, R², R^(3a) and R⁵ are as defined above,

which comprises reacting a 3-hydroxypyrazole derivative of the generalformula (3a),

wherein R¹, R² and R^(3a) are as defined above, and a compound of thegeneral formula (4),R⁵—Z  (4)

wherein R⁵ is as defined above and Z is a leaving group,

in the presence of a base.

Further, the present invention is directed to a process for thepreparation of a pyrazole derivative of the general formula (1c),

wherein R¹, R², R^(3a), R⁵ and Y are as defined above, and R^(4a) is anoptionally substituted alkyl group having 1 to 12 carbon atoms, anoptionally substituted cycloalkyl group having 3 to 8 carbon atoms, anoptionally substituted aralkyl group having 7 to 11 carbon atoms, anoptionally substituted alkenyl group having 3 to 6 carbon atoms or anoptionally substituted alkynyl group having 3 to 6 carbon atoms,

which comprises reacting the thus-obtained pyrazole derivative of thegeneral formula (1b),

wherein R¹, R², R^(3a), R⁵ and Y are as defined above, and a compound ofthe general formula (6),R^(4a)—Z  (6)

wherein R^(4a) is as defined above and Z is a leaving group.

Further, the present invention is directed to a process for thepreparation of a pyrazole-1-carboxamide derivative of the generalformula (1d) in the present invention,

wherein R¹, R² and R⁵ are as defined above and each of R^(3b) and R^(4b)is an optionally substituted alkyl group having 1 to 12 carbon atoms, anoptionally substituted cycloalkyl group having 3 to 8 carbon atoms, anoptionally substituted aralkyl group having 7 to 11 carbon atoms, anoptionally substituted alkenyl group having 3 to 6 carbon atoms, anoptionally substituted alkynyl group having 3 to 6 carbon atoms or anoptionally substituted phenyl group, or R^(3b) and R^(4b) may form aheterocyclic ring together with a nitrogen atom to which they bond,

which comprises reacting a pyrazole derivative of the general formula(2),

wherein R¹, R² and R⁵ are as defined above,

and carbamic acid chlorides of the general formula (7),

wherein R^(3b) and R^(4b) are as defined above, in the presence of abase.

Further, the present invention is directed to a pyrazole derivative ofthe general formula (2d),

wherein R¹, R² and R⁵ are as defined above, which is an intermediate inthe production of a pyrazole-1-carboxamide derivative in the presentinvention,

and, said pyrazole derivative can be produced by reacting a pyrazolederivative of the general formula (2),

wherein R¹, R² and R⁵ are as defined above, with phosgene or a materialequivalent to phosgene.

Further, the present invention is directed to a process for thepreparation of a pyrazole-1-carboxamide derivative of the generalformula (1e) in the present invention,

wherein R¹, R², R⁴ and R⁵ are as defined above and R^(3c) is a hydrogenatom, an optionally substituted alkyl group having 1 to 12 carbon atoms,an optionally substituted cycloalkyl group having 3 to 8 carbon atoms,an optionally substituted aralkyl group having 7 to 11 carbon atoms, anoptionally substituted alkenyl group having 3 to 6 carbon atoms, anoptionally substituted alkynyl group having 3 to 6 carbon atoms, anoptionally substituted phenyl group, an optionally substituted alkyloxygroup having 1 to 6 carbon atoms, an optionally substitutedcycloalkyloxy group having 3 to 8 carbon atoms, an optionallysubstituted aralkyloxy group having 7 to 11 carbon atoms, an optionallysubstituted alkenyloxy group having 3 to 6 carbon atoms, an optionallysubstituted alkynyloxy group having 3 to 6 carbon atoms or an optionallysubstituted phenyloxy group, or R^(3c) and R⁴ may form a heterocyclicring together with a nitrogen atom to which they bond,

which comprises reacting a pyrazole derivative of the general formula(2d) as an intermediate in production,

wherein R¹, R² and R⁵ are as defined above, with amines of the generalformula (8).

wherein R^(3c) and R⁴ are as defined above, optionally in the presenceof a base.

Further, the present invention is directed to a process for thepreparation of a pyrazole derivative of the general formula (1g),

wherein R¹, R³, R⁴, R⁵ and Y are as defined above and R^(2b) is ahalogen atom,

which comprises halogenating a pyrazole derivative of the generalformula (1f),

wherein R¹, R³, R⁴, R⁵ and Y are as defined above.

Further, the present invention is directed to a process for thepreparation of a pyrazole-1-carboxamide derivative of the generalformula (1i),

wherein R¹, R², R³, R⁴ and R⁵ are as defined above,

which comprises oxidizing a pyrazole-1-carbothioamide derivative of thegeneral formula (1h),

wherein R¹, R², R³, R⁴ and R⁵ are as defined above.

Further, the present invention is directed to a herbicide containing, asan active ingredient, a pyrazole derivative of the general formula (1),

wherein R¹, R², R³, R⁴, R⁵ and Y are as defined above.

PREFERRED EMBODIMENTS OF THE INVENTION

In compounds of the present invention, definitions of substituentsrepresented by R¹ to R⁵, Y and Z are as follows.

The alkyl group having 1 to 6 carbon atoms, represented by R¹, R² andR^(2a), may be linear or branched, and examples thereof include methyl,ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, tert-butyl, pentyl,isoamyl, neopentyl, 1-ethylpropyl, 1-methylbutyl, 2-methylbutyl, hexyl,isohexyl, 2-ethylbutyl and 4-methylpentyl. The above alkyl group mayhave at least one substituent such as a halogen atom, an alkyloxy grouphaving 1 to 6 carbon atoms, a formyl group, an alkyloxycarbonyl grouphaving 1 to 6 carbon atoms or a heterocyclic ring. More specifically,examples of such alkyl groups include trichloromethyl, trifluoromethyl,methoxymethyl, ethoxymethyl, 2-methoxyethyl, formylmethyl,methoxycarbonylmethyl, ethoxycarbonylmethyl, furfuryl,tetrahydrofurfuryl, 2-picolyl, 3-picolyl, 4-picolyl, 2-thienylmethyl and2-morpholinoethyl.

The alkyl group having 1 to 12 carbon atoms, represented by R³, R^(3a),R^(3b), R^(3c), R⁴, R^(4a) and R^(4b), may be linear or branched, andexamples thereof include methyl, ethyl, propyl, isopropyl, butyl,isobutyl, s-butyl, tert-butyl, pentyl, isoamyl, neopentyl,1-ethylpropyl, 1-methylbutyl, 2-methylbutyl, hexyl, isohexyl,2-ethylbutyl, 4-methylpentyl, heptyl, 1-methylhexyl, octyl, decyl,undecyl and dodecyl. The above alkyl group may have at least onesubstituent such as a halogen atom, a cycloalkyl group having 3 to 8carbon atoms, a cyano group, a nitro group, an alkylthio group having 1to 6 carbon atoms, an alkyloxy group having 1 to 6 carbon atoms, analkyloxycarbonyl group having 1 to 6 carbon atoms, a carboxy group or anacyl group. More specifically, examples of such alkyl groups include2-chloroethyl, 2-bromoethyl, 3-chloropropyl, 3-fluoropropyl,cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyanomethyl,2-cyanoethyl, 3-cyanopropyl, nitromethyl, 2-methylthioethyl,methoxymethyl, ethoxymethyl, 2-methoxyethyl, 2-chloroethoxymethyl,methoxycarbonylmethyl, ethoxycarbonylmethyl, 1-methoxycarbonylethyl,1-ethoxycarbonylethyl, 2-ethoxycarbonylethyl, carboxymethyl, acetonyl,1-acetylethyl, 3-acetylpropyl, phenacyl, 4-chlorophenacyl,2,4-difluorophenacyl, 4-methylphenacyl, 4-isopropylphenacyl,4-isobutylphenacyl, 4-cyclohexylphenacyl, 4-cyanophenacyl and4-nitrophenacyl.

Examples of the cycloalkyl group having 3 to 8 carbon atoms, representedby R¹, R³, R^(3a), R^(3b), R^(3c), R⁴, R^(4a) and R^(4b), includecyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cyclooctyl. Theabove cycloalkyl group may have a substituent such as a halogen atom, analkyl group having 1 to 4 carbon atoms, an alkyloxycarboyl group having1 to 4 carbon atoms or a cyano group. More specifically, examples ofsuch cycloalkyl groups include 1-methylcyclopropyl,2,2-dimethylcyclopropyl, 2-chlorocyclopropyl, 2,2-dichlorocyclopropyl,2-methoxycarbonylcyclopropyl, 2-cyanocyclopropyl, 2-methylcyclopentyland 3-methylcyclopentyl.

Examples of the aralkyl group having 7 to 11 carbon atoms, representedby R³, R^(3a), R^(3b), R^(3c), R⁴, R^(4a) and R^(4b), include benzyl,1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, 1-naphthylmethyl and2-naphthylmethyl. The above aralkyl group may have, on its aromaticring, at least one substituent such as a halogen atom, an alkyl grouphaving 1 to 12 carbon atoms, a haloalkyl group having 1 to 6 carbonatoms, an alkyloxy group having 1 to 6 carbon atoms, a haloalkyloxygroup having 1 to 6 carbon atoms, an alkylthio group having 1 to 6carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, analkyloxycarbonyl group having 1 to 6 carbon atoms, an carboxy group, anoptionally substituted carbamoyl group, a cyano group or a nitro group.More specifically, examples of such aralkyl groups include benzyl,2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-chlorobenzyl,3-chlorobenzyl, 4-chlorobenzyl, 2-bromobenzyl, 3-bromobenzyl,4-bromobenzyl, 3,5-difluorobenzyl, 3,5-dichlorobenzyl,3,5-dibromobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl,2,4-dimethylbenzyl, 3,5-dimethylbenzyl, 2-trifluoromethylbenzyl,3-trifluoromethylbenzyl, 4-trifluoromethylbenzyl,3,5-bis(trifluoromethyl)benzyl, 2,4-bis(trifluoromethyl)benzyl,2-methoxycarbonylbenzyl, 3-methoxycarbonylbenzyl,4-methoxycarbonylbenzyl, 3-carboxybenzyl, 4-carboxybenzyl,3-(N,N-dimethylcarbamoyl)benzyl, 4-(N,N-dimethylcarbamoyl)benzyl,3-(N,N-diethylcarbamoyl)benzyl, 3-(N-ethyl-N-propylcarbamoyl)benzyl,3-cyanobenzyl, 4-cyanobenzyl, 2-methoxybenzyl, 3-methoxybenzyl,4-methoxybenzyl, 3,4-dimethoxybenzyl, 4-trifluoromethoxybenzyl,4-phenoxybenzyl, 4-methylthiobenzyl, 4-methylsulfonylbenzyl,2-nitrobenzyl, 3-nitrobenzyl, 4-nitrobenzyl, 1-(2-fluorophenyl)ethyl,1-(2-chlorophenyl)ethyl, 1-(2-bromophenyl)ethyl,1-(3-fluorophenyl)ethyl, 1-(3-chlorophenyl)ethyl,1-(3-bromophenyl)ethyl, 1-(4-fluorophenyl)ethyl,1-(4-chlorophenyl)ethyl, 1-(4-bromophenyl)ethyl,1-(2-trifluoromethylphenyl)ethyl, 1-(3-trifluoromethylphenyl)ethyl,1-(4-trifluoromethylphenyl)ethyl, 2-(3-bromophenyl)ethyl,2-(3-trifluoromethylphenyl)ethyl, 3-phenylpropyl and 4-phenylbutyl.

Examples of the alkenyl group having 3 to 6 carbon atoms, represented byR³, include allyl, 2-methyl-2-propenyl, 2-butenyl, 3-butenyl,2-pentenyl, 3-pentenyl, 2-hexenyl and 3-hexenyl. The alkenyl group maybe substituted with a halogen atom or the like. Examples of thesubstituted alkenyl group include 2-chloro-2-propenyl, 3-chloropropenyland 4-chloro-2-butenyl.

Examples of the alkenyl group having 3 to 6 carbon atoms, represented byR^(3a), R^(3b), R^(3c), R⁴, R^(4a) and R^(4b), include allyl,2-methyl-2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl,2-hexenyl and 3-hexenyl. The alkenyl group may be substituted with ahalogen atom or the like. Examples of the substituted alkenyl groupinclude 2-chloro-2-propenyl, 3-chloropropenyl and 4-chloro-2-butenyl.

The alkynyl group having 3 to 6 carbon atoms, represented by R³, R^(3a),R^(3b), R^(3c), R⁴, R^(4a) and R^(4b), may be linear or branched, andexamples thereof include propargyl, 1-butyn-3-yl, 3-methyl-1-butyn-3-yl,2-butynyl, 2-pentynyl and 3-pentynyl. The alkynyl group may besubstituted with a halogen atom, or the like. Examples of thesubstituted alkynyl group include 3-fluoro-2-propynyl,3-chloro-2-propynyl, 3-bromo-2-propynyl, 4-bromo-2-butynyl and4-bromo-3-butynyl.

The optionally substituted phenyl group represented by R¹, R³, R^(3a),R^(3b), R^(3c), R⁴ and R^(4b) is, for example, a phenyl group having, asa substituent on a benzene ring, a halogen atom, an alkyl group having 1to 12 carbon atoms, a haloalkyl group having 1 to 6 carbon atoms, anacyl group having 1 to 6 carbon atoms, an alkyl group having 1 to 12carbon atoms and being substituted with an alkyloxyimino group having 1to 4 carbon atoms, an alkyloxycarbonyl group having 1 to 6 carbon atoms,a carboxy group, a cyano group, an alkyloxy group having 1 to 6 carbonatoms, an aryloxy group, a haloalkyloxy group having 1 to 6 carbonatoms, an alkylthio group having 1 to 6 carbon atoms, an alkylsulfinylgroup having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6carbon atoms, a haloalkylthio group having 1 to 6 carbon atoms, ahaloalkylsulfinyl group having 1 to 6 carbon atoms, a haloalkylsulfonylgroup having 1 to 6 carbon atoms or a nitro group. More specifically,examples of such optionally substituted phenyl group include2-fluorophenyl, 2-chlorophenyl, 2-bromophenyl, 3-fluorophenyl,3-chlorophenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl,2,4-difluorophenyl, 2,4-dichlorophenyl, 3,5-difluorophenyl,3,5-dichlorophenyl, 3-chloro-2,4-difluorophenyl, 2,4,5-trichlorophenyl,2,4-dichloro-3-methylphenyl, 2,4-dichloro-5-methoxyphenyl,2,4-dichloro-5-isopropyloxyphenyl, 2-fluoro-4-chloro-5-methoxyphenyl,2-fluoro-4-chloro-5-isopropyloxyphenyl,2-fluoro-4-chloro-5-cyclopentyloxyphenyl,2-fluoro-4-chloro-5-propargyloxyphenyl,2-fluoro-4-chloro-5-(1-butyn-3-yloxy)phenyl,2-fluoro-4-trifluoromethylphenyl, 2-chloro-4-trifluoromethylphenyl,2-chloro-5-trifluoromethylphenyl, 4-fluoro-3-phenoxyphenyl,2-fluoro-5-nitrophenyl, 2,4-difluoro-5-nitrophenyl, 2-methylphenyl,3-methylphenyl, 4-methylphenyl, 2,4-dimethylphenyl, 4-ethylphenyl,4-isopropylphenyl, 4-tert-butylphenyl, 2-trifluoromethylphenyl,3-trifluoromethylphenyl, 4-trifluoromethylphenyl,2,4-bis(trifluoromethyl)phenyl, 3,5-bis(trifluoromethyl)phenyl,2-acetylphenyl, 4-acetylphenyl, 4-isovalerylphenyl,2-methoxycarbonylphenyl, 2-ethoxycarbonylphenyl,3-methoxycarbonylphenyl, 4-methoxycarbonylphenyl, 2-carboxyphenyl,4-carboxyphenyl, 2-cyanophenyl, 4-cyanophenyl, 2-methoxyphenyl,3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl,4-isopropyloxyphenyl, 4-tert-butyloxyphenyl, 3-trifluoromethyloxyphenyl,4-trifluoromethyloxyphenyl, 3-phenoxyphenyl, 4-phenoxyphenyl,2-methylthiophenyl, 4-methylthiophenyl, 2-methylsulfinylphenyl,4-methylsulfinylphenyl, 2-methylsulfonylphenyl, 4-methylsulfonylphenyl,4-trifluoromethylthiophenyl, 4-trifluoromethylsulfinylphenyl,4-trifluoromethylsulfonylphenyl, 2-nitrophenyl and 4-nitrophenyl.

The optionally substituted phenyl group represented by R⁵ and R^(5a) is,for example, a phenyl group having, as a substituent on a benzene ring,a halogen atom, an alkyl group having 1 to 12 carbon atoms, a haloalkylgroup having 1 to 6 carbon atoms, an acyl group having 1 to 6 carbonatoms, an alkyl group having 1 to 12 carbon atoms and being substitutedwith an alkyloxyimino group having 1 to 4 carbon atoms, analkyloxycarbonyl group having 1 to 6 carbon atoms, a carboxy group, acyano group, a substituted amino group, an alkyloxy group having 1 to 6carbon atoms, an aryloxy group, a haloalkyloxy group having 1 to 6carbon atoms, an alkylthio group having 1 to 6 carbon atoms, analkylsulfinyl group having 1 to 6 carbon atoms, an alkylsulfonyl grouphaving 1 to 6 carbon atoms, a haloalkylthio group having 1 to 6 carbonatoms, a haloalkylsulfinyl group having 1 to 6 carbon atoms, ahaloalkylsulfonyl group having 1 to 6 carbon atoms or a nitro group. Asa substituent on a benzene ring, electron-withdrawing groups such as atrifluoromethyl group, a nitro group, a cyano group, a chlorine atom, afluorine atom and an alkyloxycarbonyl group are preferred, since a goodreaction yield is attained and since raw materials can be easilyobtained. Further, such electron-withdrawing groups are preferablysubstituted at an o-position and/or p-position. More specifically,examples of the above substituted phenyl include 4-fluorophenyl,4-chlorophenyl, 4-bromophenyl, 2,4-difluorophenyl, 2,4-dichlorophenyl,2,4,5-trichlorophenyl, 2-chloro-5-trifluoromethylphenyl,2-trifluoromethylphenyl, 4-trifluoromethylphenyl,2,4-bis(trifluoromethyl)phenyl, 2,6-dichloro-4-trifluoromethylphenyl,4-cyanophenyl, 4-cyano-2-trifluoromethylphenyl, 2-methylthiophenyl,4-methylthiophenyl, 2-methylsulfinylphenyl, 4-methylsulfinylphenyl,2-methylsulfonylphenyl, 4-methylsulfonylphenyl,4-trifluoromethylthiophenyl, 4-trifluoromethylsulfinylphenyl,4-trifluoromethylsulfonylphenyl, 2-nitrophenyl, 4-nitrophenyl,2-nitro-4-trifluoromethylphenyl, 4-nitro-2-trifluoromethylphenyl,4-nitro-3-trifluoromethylphenyl, 2,6-dichloro-4-trifluoromethylphenyl,2-chloro-6-fluoro-4-trifluoromethylphenyl,2-chloro-6-nitro-4-trifluoromethylphenyl and2,4-dinitro-6-trifluoromethylphenyl. Concerning these substituents on abenzene ring, for example, a nitro group is convertible to an aminogroup by reduction, and the amino group is further convertible to ahalogen atom or a substituted alkyl group through a diazonium salt, andthese can be included in the substituents on a benzene ring.

The optionally substituted pyridyl group represented by R⁵ and R^(5a)is, for example, a pyridyl group having, as a substituent on a pyridinering, a halogen atom, an alkyl group having 1 to 12 carbon atoms, ahaloalkyl group having 1 to 6 carbon atoms, an acyl group having 1 to 6carbon atoms, an alkyl group having 1 to 12 carbon atoms and beingsubstituted with an alkyloxyimino group having 1 to 4 carbon atoms, analkyloxycarbonyl group having 1 to 6 carbon atoms, a carboxy group, acyano group, an alkyloxy group having 1 to 6 carbon atoms, an aryloxygroup, a haloalkyloxy group having 1 to 6 carbon atoms, an alkylthiogroup having 1 to 6 carbon atoms, an alkylsulfinyl group having 1 to 6carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, ahaloalkylthio group having 1 to 6 carbon atoms, a haloalkylsulfinylgroup having 1 to 6 carbon atoms, a haloalkylsulfonyl group having 1 to6 carbon atoms or a nitro group. As a substituent on a pyridine ring,electron-withdrawing groups such as a trifluoromethyl group, a nitrogroup, a cyano group, a chlorine atom, a fluorine atom and analkyloxycarbonyl group are preferred, since a good reaction yield isattained and since raw materials can be easily obtained. Further, suchelectron-withdrawing groups are preferably substituted at the 3-positionand/or the 5-position of a pyridine ring. More specifically, examples ofthe substituted pyridyl group include 3-chloropyridin-2-yl,5-chloropyridin-2-yl, 3,5-dichloropyridin-2-yl,4-amino-3,5-dichloropyridin-2-yl, 3-cyano-6-methylpyridin-2-yl,5-trifluoromethylpyridin-2-yl, 3-chloro-5-trifluoromethylpyridin-2-yl,3-nitropyridin-2-yl, 5-nitropyridin-2-yl, 3-nitro-4-methylpyridin-2-yl,3-nitro-6-methoxypyridin-2-yl, 2-chloro-3-nitropyridin-6-yl,6-chloro-3-nitropyridin-2-yl and 3,5-dinitropyridin-2-yl. Concerningthese substituents on a pyridine ring, for example, a nitro group isconvertible to an amino group by reduction, and the amino group isfurther convertible to a halogen atom or a substituted alkyl groupthrough a diazonium salt, and these can be included in the substituentson a pyridine ring.

Examples of the alkyloxy group having 1 to 6 carbon atoms, representedby R³, R^(3a) and R^(3c), include methoxy, ethoxy, propyloxy,isopropyloxy, butyloxy, isobutyloxy, sec-butyloxy, tert-butyloxy,pentyloxy and hexyloxy. The alkyl group constituting such an alkyloxygroup may be substituted with at least one of a halogen atom, acycloalkyl group having 3 to 8 carbon atoms, an alkyloxy group having 1to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, analkyloxycarbonyl group having 1 to 6 carbon atoms, a carboxy group, acyano group, a nitro group, an optionally substituted amino group and anoptionally substituted phenyl group.

Examples of the cycloalkyloxy group having 3 to 8 carbon atoms,represented by R³, R^(3a) and R^(3c), include cyclopropyloxy,cyclobutyloxy, cyclopentyloxy, cyclohexyloxy and cyclooctyloxy. Thesecycloalkyl groups may be substituted with a halogen atom, an alkyl grouphaving 1 to 4 carbon atoms, an alkyloxycarbonyl group having 1 to 4carbon atoms or a cyano group. More specifically, examples of suchsubstituted cycloalkyloxy groups include 1-methylcyclopropyloxy,2,2-dimethylcyclopropyloxy, 2-chlorocyclopropyloxy,2,2-dichlorocyclopropyloxy, 2-methoxycarbonylcyclopropyloxy,2-cyanocyclopropyloxy, 2-methylcyclopentyloxy and3-methylcyclopentyloxy.

Examples of the aralkyloxy group having 7 to 11 carbon atoms,represented by R³, R^(3a) and R^(3c), include benzyloxy,1-phenylethyloxy, 2-phenylethyloxy, 1-phenylpropyloxy,1-naphthylmethyloxy and 2-naphthylmethyloxy. The aromatic ring of thearalkyloxy group may be substituted with at least one of a halogen atom,an alkyl group having 1 to 12 carbon atoms, a haloalkyl group having 1to 6 carbon atoms, an alkyloxy group having 1 to 6 carbon atoms, ahaloalkyloxy group having 1 to 6 carbon atoms, an alkylthio group having1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms,an alkyloxycarbonyl group having 1 to 6 carbon atoms, a carboxy group,an optionally substituted carbamoyl group, a cyano group and a nitrogroup.

The alkenyloxy group having 3 to 12 carbon atoms, represented by R³,R^(3a) and R^(3c), may be linear or branched, and examples thereofinclude 1-propenyloxy, allyloxy, 2-methyl-2-propenyloxy, 2-butenyloxy,3-butenyloxy, 2-pentenyloxy, 3-pentenyloxy, 1-cyclopentenyloxy,2-hexenyloxy, 3-hexenyloxy, 1-cyclohexenyloxy, 2-heptenyloxy and1-cyclooctenyloxy. The alkenyloxy group may be substituted with ahalogen atom, or the like, and examples of the substituted alkenyloxygroup include 2-chloro-2-propenyloxy, 3-chloropropenyloxy and4-chloro-2-butenyloxy.

The alkynyloxy group having 3 to 6 carbon atoms, represented by R³,R^(3a) and R^(3c), may be linear or branched, and examples thereofinclude propargyloxy, 1-butyn-3-yloxy, 3-methyl-1-butyn-3-yloxy,2-butynyloxy, 2-pentynyloxy and 3-pentynyloxy. The above alkynyloxygroup may be substituted with a halogen atom, or the like, and examplesof the substituted alkynyloxy group include 3-fluoro-2-propynyloxy,3-chloro-2-propynyloxy, 3-bromo-2-propynyloxy, 4-bromo-2-butynyloxy and4-bromo-3-butynyloxy.

Examples of the heterocyclic ring that a combination of R³ and R⁴, acombination of R^(3c) and R⁴ or a combination of R^(3b) and R^(4b) formstogether with a nitrogen atom to which they bond include pyrrole,pyrroline, pyrrolidine, imidazole, imidazoline, imidazolioine, pyrazole,pyrazoline, pyrazolidine, piperidine, piperazine, indole, indoline,isoindole, 1H-indazole, purine, oxazoline, isoxazoline, isoxazolidine,thiazoline, morpholine, thiomorpholine, aziridine, azocane andtetrahydrooxazine. The above heterocyclic ring may be substituted withat least one of an alkyl group having 1 to 6 carbon atoms, a haloalkylgroup having 1 to 6 carbon atoms, a halogen atom and a cyano group.

Examples of the halogen atom represented by R² and R^(2b) include achlorine atom, a bromine atom and a fluorine atom.

Examples of the leaving group represented by Z include halogen atomssuch as a chlorine atom, a bromine atom and iodine atom and alkyl- orarylsulfonyloxy groups such as methylsulfonyloxy,trifluoromethylsulfonyloxy, phenylsulfonyloxy and p-tolylsulfonyloxy.

The method of producing the pyrazole derivative of the present inventionand the intermediate thereof will be explained in detail below.

Production method-1 (Step-1) shows a method in which a reaction of apyrazole derivative (3) and a compound (4) is carried out in thepresence of a base, to produce a pyrazole derivative (2) of the presentinvention.

[Production Method-1]

wherein R¹, R², R⁵ and Z are as defined above.

The above reaction is essentially carried out in the presence of a base.The base can be selected from alkali metal bases such as sodium hydride,sodium amide, sodium carbonate, potassium carbonate, sodium methoxide,sodium ethoxide, potassium-t-butoxide, sodium hydroxide and potassiumhydroxide, and organic amines such as triethylamine, tributylamine,N-methylmorpholine, pyridine and dimethylaniline. The base is preferablyused in an amount of one to excess equivalents to the reactionsubstrate, since a good yield is attained.

The reaction is preferably carried out in a solvent, and any solvent canbe used so long as it has no adversary effect on the reaction. Forexample, the solvent can be selected from ether solvents such as diethylether, tetrahydrofuran (THF), dioxane and 1,2-dimethoxyethane (DME),nitriles such as acetonitrile and propionitrile, esters such as ethylacetate and ethyl propionate, aromatic hydrocarbon solvents such asbenzene, toluene, xylene and chlorobenzene, amides such asN,N-dimethylformamide (DMF) and N-methylpyrrolidone, dimethylsulfoxide(DMSO), water or mixtures of these. While the reaction temperature isnot specially limited, the desired product can be obtained in good yieldby carrying out the reaction at a temperature that is determined in therange of 0° C. to 150° C. as required. After completion of the reaction,the desired product can be obtained by ordinary post-treatmentprocedures. The product can be purified by column chromatography orrecrystallization as required.

The pyrazole derivative represented by the general formula (3), as a rawmaterial in the above step, can be easily prepared by a cyclizationreaction of hydrazine and a β-ketoester derivative as described, forexample, in Organic Synthesis Vol. 6, 791 (1988). While thethus-obtained 3-hydroxypyrazole derivative (3) is present in the form ofan equilibrium mixture with a tautomer, the general formula shows astructure of an alcohol form (3) for the convenience.

Production method-2 (step-2) is a method in which a pyrazole derivative(2a) is halogenated to produce a pyrazole derivative (2b) of the presentinvention.

wherein R¹, R^(2a) and R^(5a) are as defined above.

The halogenation can be carried out with a halogenating reagent. Thehalogenating reagent can be selected from sulfuryl chloride,N-chlorosuccinimide or N-bromosuccinimide.

The reaction is preferably carried out in a solvent, and any solvent canbe used so long as it has no adversary effect on the reaction. Examplesof the solvent include aliphatic hydrocarbon solvents such as pentane,hexane and octane, ether solvents such as diethyl ether,tetrahydrofuran, dioxane and DME, halogen-containing solvents such asdichloromethane, chloroform and carbon tetrachloride, aromatichydrocarbon solvents such as chlorobenzene and dichlorobenzene, organicacid solvents such as acetic acid and propionic acid, water and mixturesof these.

While the reaction temperature differs depending upon the halogenatingreagent used, it is determined at a temperature in the range of −10° C.to 150° C. The reaction is preferably carried out at a temperaturedetermined in the range of 0° C. to the reflux temperature of a solventas required, since it gives a good yield. After completion of thereaction, the desired product can be obtained by ordinary post-treatmentprocedures. The product can be purified by column chromatography orrecrystallization as required.

Production method-3 (step-3) is a step in which a pyrazole derivative(2c) reacts with isocyanates or isothiocyanates (5), to produce apyrazole derivative (1a) of the present invention.

wherein R¹, R², R^(3a), R^(5a) and Y are as defined above.

The above reaction can be carried out in the presence of a base, and thebase can be selected from alkali metal bases such as sodium hydride,sodium amide, sodium carbonate, potassium carbonate, sodium methoxide,sodium ethoxide, potassium-t-butoxide, sodium hydroxide and potassiumhydroxide, and organic amines such as triethylamine, tributylamine,N-methylmorpholine, pyridine and dimethylaniline. The amount of the baseis not specially limited.

The reaction can be carried out in a solvent, and any solvent can beused so long as it has no adversary effect on the reaction. Examples ofthe solvent include ether solvents such as diethyl ether, THF, dioxaneand DME, nitriles such as acetonitrile and propionitrile, esters such asethyl acetate and ethyl propionate, aromatic hydrocarbon solvents suchas benzene, toluene, xylene and chlorobenzene, halogen-containingsolvents such as dichloromethane, chloroform and carbon tetrachloride,amides such as DMF and N-methylpyrrolidone, DMSO or mixtures of these.While the reaction temperature is not specially limited, the desiredproduct can be obtained in good yield by carrying out the reaction at atemperature that is determined in the range of 0° C. to 150° C. asrequired. After completion of the reaction, the desired product can beobtained by ordinary post-treatment procedures. The product can bepurified by column chromatography or recrystallization as required.

Production-4 (step-4) shows a method in which a reaction of a pyrazolederivative (3a) and a compound (4) is carried out in the presence of abase, to produce a pyrazole derivative (1b) of the present invention.

wherein R¹, R², R^(3a), R⁵ and Z are as defined above.

It is essential to carry out the above reaction in the presence of abase. The base can be selected from alkali metal bases such as sodiumhydride, sodium amide, sodium carbonate, potassium carbonate, sodiummethoxide, sodium ethoxide, potassium-t-butoxide, sodium hydroxide andpotassium hydroxide, and organic amines such as triethylamine,tributylamine, N-methylmorpholine, pyridine and dimethylaniline. Thebase is preferably used in an amount of one to excess equivalents to thereaction substrate, since a good yield is attained.

The reaction is preferably carried out in a solvent, and any solvent canbe used so long as it has no adversary effect on the reaction. Forexample, the solvent can be selected from ether solvents such as diethylether, tetrahydrofuran (THF), dioxane and 1,2-dimethoxyethane (DME),nitriles such as acetonitrile and propionitrile, esters such as ethylacetate and ethyl propionate, aromatic hydrocarbon solvents such asbenzene, toluene, xylene and chlorobenzene, amides such asN,N-dimethylformamide (DMF) and N-methylpyrrolidone, dimethylsulfoxide(DMSO), water or mixtures of these. While the reaction temperature isnot specially limited, the desired product can be obtained in good yieldby carrying out the reaction at a temperature that is determined in therange of 0° C. to 150° C. as required. After completion of the reaction,the desired product can be obtained by ordinary post-treatmentprocedures. The product can be purified by column chromatography orrecrystallization as required.

Production method-5 (step-5) shows a method in which a reaction of apyrazole derivative (1b) and a compound (6) is carried out in thepresence of a base, to produce a pyrazole derivative (1c) of the presentinvention.

wherein R¹, R², R^(3a), R^(4a), R⁵, Y and Z are as defined above.

It is essential to carry out the above reaction in the presence of abase. The base can be selected from alkali metal bases such as sodiumhydride, sodium amide, sodium carbonate, potassium carbonate, sodiummethoxide, sodium ethoxide, potassium-t-butoxide, sodium hydroxide andpotassium hydroxide, and organic amines such as triethylamine,tributylamine, N-methylmorpholine, pyridine and dimethylaniline. Whenthe base is used in an amount of one to excess equivalents to thereaction substrate, the desired product can be obtained in good yield.

The reaction is preferably carried out in a solvent, and any solvent canbe used so long as it has no adversary effect on the reaction. Examplesof the solvent include ether solvents such as diethyl ether, THF, DMEand dioxane, nitriles such as acetonitrile and propionitrile, aromatichydrocarbon solvents such as benzene, toluene, xylene and chlorobenzene,amides such as DMF and N-methylpyrrolidone, DMSO, water or mixtures ofthese. While the reaction temperature is not specially limited, thedesired product can be obtained in good yield by carrying out thereaction at a temperature that is determined in the range of 0° C. to100° C. as required. After completion of the reaction, the desiredproduct can be obtained by ordinary post-treatment procedures. Theproduct can be purified by column chromatography or recrystallization asrequired.

Production method-6 (step-6) shows a method in which a reaction of apyrazole derivative (2) and a carbamic acid chlorides (7) is carried outin the presence of a base, to produce a pyrazole derivative (1d) of thepresent invention.

wherein R¹, R², R^(3b), R^(4b) and R⁵ are as defined above.

It is essential to carry out the above reaction in the presence of abase. The base can be selected from alkali metal bases such as sodiumhydride, sodium amide, sodium carbonate, potassium carbonate, sodiummethoxide, sodium ethoxide, potassium-t-butoxide, sodium hydroxide andpotassium hydroxide, and organic amines such as triethylamine,tributylamine, N-methylmorpholine, pyridine and dimethylaniline. Whenthe base is used in an amount of one to excess equivalents to thereaction substrate, the desired product can be obtained in good yield.

The reaction is preferably carried out in a solvent, and any solvent canbe used so long as it has no adversary effect on the reaction. Examplesof the solvent include ether solvents such as diethyl ether, THF, DMEand dioxane, nitriles such as acetonitrile and propionitrile, aromatichydrocarbon solvents such as benzene, toluene, xylene and chlorobenzene,amides such as DMF and N-methylpyrrolidone, DMSO, water or mixtures ofthese. While the reaction temperature is not specially limited, thedesired product can be obtained in good yield by carrying out thereaction at a temperature that is determined in the range of 0° C. to100° C. as required. After completion of the reaction, the desiredproduct can be obtained by ordinary post-treatment procedures. Theproduct can be purified by column chromatography or recrystallization asrequired.

Production method-7 shows a method in which a pyrazole derivative (2)reacts with phosgene or a phosgene equivalent material such as aphosgene dimer or a phosgene trimer to prepare a pyrazole derivative(2d) of the present invention which is a production intermediate(step-7) and then the pyrazole derivative (2d) reacts with amines (8) inthe presence of a base, to produce a pyrazole derivative (1e) of thepresent invention (step-8).

wherein R¹, R², R^(3c), R⁴ and R⁵ are as defined above.

In the reaction in the step-7, the pyrazole derivative (2) reacts withphosgene or a phosgene equivalent material in a halogen-containingsolvent such as dichloromethane, chloroform or carbon tetrachloride, anaromatic hydrocarbon solvent such as benzene, toluene, xylene orchlorobenzene or an ester solvent such as ethyl acetate or propylacetate, whereby the desired product can be synthesized. While thereaction temperature is not specially limited, the desired product canbe obtained in good yield by carrying out the reaction at a temperaturethat is determined in the range of −30° C. to 150° C. as required. Aftercompletion of the reaction, the desired product can be obtained byordinary post-treatment procedures. The product can be used for thesubsequent reaction without its isolation.

It is essential to carry out the react-on in the step-8 in the presenceof a base. The base can be selected from alkali metal bases such assodium hydride, sodium amide, sodium carbonate, potassium carbonate,potassium-t-butoxide, sodium hydroxide and potassium hydroxide, andorganic amines such as triethylamine, tributylamine, N-methylmorpholine,pyridine and dimethylaniline. The base is used in an amount of one toexcess equivalents to the reaction substrate, whereby the desiredproduct can be obtained in good yield.

The reaction is preferably carried out in an organic solvent, and thesolvent can be selected from benzene, toluene, xylene, THF, diethylether, chloroform, dichloromethane, methanol, ethanol, propyl alcohol,isopropyl alcohol, tert-butyl alcohol, ethyl acetate, DMF or DMSO. Thereaction can be carried out at a temperature that is determined in therange of room temperature to the reflux temperature of a solvent asrequired. After completion of the reaction, the desired product can beobtained by ordinary post-treatment procedures. The product can bepurified by column chromatography or recrystallization as required.

Production method-8 (step 9) shows a method in which a pyrazolederivative (1f) is halogenated to produce a pyrazole derivative (1g) ofthe present invention.

[Production Method-8]

wherein R¹, R^(2b), R³, R⁴, R⁵ and Y are as defined above.

The halogenation can be carried out with a halogenating reagent. Thehalogenating reagent can be selected from sulfuryl chloride,N-chlorosuccinimide or N-bromosuccinimide.

The reaction is preferably carried out in a solvent, and any solvent canbe used so long as it has no adversary effect on the reaction. Examplesof the solvent include aliphatic hydrocarbon solvents such as pentane,hexane and octane, ether solvents such as diethyl ether,tetrahydrofuran, dioxane and DME, halogen-containing solvents such asdichloromethane, chloroform and carbon tetrachloride, aromatichydrocarbon solvents such as chlorobenzene and dichlorobenzene, organicacid solvents such as acetic acid and propionic acid, water and mixturesof these.

While the reaction temperature differs depending upon the halogenatingreagent used, it is determined at a temperature in the range of −10° C.to 150° C. The reaction is preferably carried out at a temperaturedetermined in the range of 0° C. to the reflux temperature of a solventas required, since a good yield is attained. After completion of thereaction, the desired product can be obtained by ordinary post-treatmentprocedures. The product can be purified by column chromatography orrecrystallization as required.

Production method-9 (step-10) shows a method in which a thiocarbonylgroup of a pyrazole derivative (1 h) is oxidized to produce a pyrazolederivative (1i) of the present invention.

[Production Method-9]

wherein R¹, R², R³, R⁴ and R⁵ are as defined above.

The thiocarbonyl group can be oxidized with an oxidizing reagent. As anoxidizing reagent, for example, hydrogen peroxide can be used.

The reaction is preferably carried out in an aqueous alcohol with asuitable water-concentration. The alcohol can be selected from methanol,ethanol or propanol. The above reaction is preferably carried out in thepresence of a base, and the base can be selected from sodium hydroxideor potassium hydroxide. The reaction can be carried out at a temperaturethat is determined in the range of −30° C. to 60° C. as required. Aftercompletion of the reaction, the desired product can be obtained byordinary post-treatment procedures. The product can be purified bycolumn chromatography or recrystallization as required.

The present invention will be explained further in detail with referenceto Referential Examples and Examples hereinafter, while the presentinvention shall not be limited thereto.

EXAMPLES Referential Example 1

Hydrazine monohydrate (10.0 g, 20.0 mmol) was added to a solution ofethyl 3-oxobutanoate (26.0 g, 20.0 mmol) in ethanol (50 ml) at 0° C.,and the mixture was stirred at room temperature for 1 hour. Aftercompletion of the reaction, a precipitated solid was filtered and washedwith diethyl ether, to give a white solid of 3-hydroxy-5-methylpyrazole(16.9 g, yield: 86.0%). mp: 215-216° C.; ¹H-NMR (DMSO-d₆, DMSO, ppm): δ2.10 (s, 3H), 5.22 (s, 1H), 8.50-11.90 (br s, 2H).

Referential Examples 2-9

Reactions of hydrazine monohydrate with β-ketoester derivative(Referential Example 2: ethyl 3-oxopentanoate, Referential Example 3:ethyl isobutylylacetate, Referential Example 4: methyl4,4-dimethyl-3-oxopentanate, Referential Example 5: methyl4-methoxyacetate, Referential Example 6: diethyl 3-oxoglutarate,Referential Example 7: ethyl 4,4,4-trifluoro-3-oxobutanate, ReferentialExample 8: ethyl 2-methyl-3-oxobutanate, Referential Example 9: ethyl2-ethyl-3-oxobutanate) were carried out in the same manner as inReferential Example 1, to give corresponding 3-hydroxypyrazolederivatives. Products/forms/yields/melting points/NMR spectra aredescribed below.

Referential Example 2

5-ethyl-3-hydroxypyrazole/white solid/yield: 74.8%/mp: 191-193°C./¹H-NMR (DMSO-d₆, DMSO, ppm): δ 1.13 (t, J=7.6 Hz, 3H), 2.46 (q, J=7.6Hz, 2H), 5.24 (s, 1H), 9.10-11.60 (br s, 1H). (Amino proton was notassigned.).

Referential Example 3

3-hydroxy-5-isopropylpyrazole/white solid/yield: 57.5%/mp: 189-193°C./¹H-NMR (DMSO-d₆, DMSO, ppm): δ 1.15 (d, J=6.9 Hz, 6H), 2.79 (sep,J=6.9 Hz, 1H), 5.23 (s, 1H), 8.80-12.40 (br s, 1H).

Referential Example 4

5-tert-butyl-3-hydroxypyrazole/white solid/yield: 74.2%/mp: 205-206°C./¹H-NMR (DMSO-d₆, DMSO, ppm): δ 1.26 (s, 9H), 5.22 (s, 1H), 8.60-12.20(br s, 2H).

Referential Example 5

3-hydroxy-5-(methoxymethyl)pyrazole/white solid/yield: 80.1%/mp:123-125° C./¹H-NMR (DMSO-d₆, DMSO, ppm): δ 3.23 (s, 3H), 4.25 (s, 2H),5.42 (s, 1H), 9.00-13.00 (m, 2H).

Referential Example 6

ethyl(3-hydroxypyrazol-5-yl)acetate/white solid/yield: 35.4%/mp:114-117° C./¹H-NMR (DMSO-d₆, DMSO, ppm): δ 1.20 (t, J=7.1 Hz, 3H), 3.34(s, 2H), 4.10 (q, J=7.1 Hz, 2H), 5.35 (s, 1H), 8.60-12.20 (m, 2H).

Referential Example 7

3-hydroxy-5-trifluoromethylpyrazole/white solid/yield: 81.5%/mp:211-215° C./¹H-NMR (DMSO-d₆, DMSO, ppm): δ 5.69 (s, 1H), 10.70-11.60(brs, 1H), 12.20-13.40 (br s, 1H).

Referential Example 8

4,5-dimethyl-3-hydroxypyrazole/white solid/yield: 93.7%/mp: 268-270°C./¹H-NMR (DMSO-d₆, DMSO, TMS, ppm): δ 1.73 (s, 3H), 2.03 (s, 3H),9.20-12.50 (br s, 2H).

Referential Example 9

4-ethyl-3-hydroxy-5-methylpyrazole/white solid/yield: 86.7%/mp: 232-234°C./¹H-NMR (DMSO-d₆, DMSO, ppm): δ 1.00 (t, J=7.5 Hz, 3H), 2.05 (s, 3H),2.21 (q, J=7.5 Hz, 2H), 8.90-11.50 (br s, 2H).

Referential Example 10

Hydrazine monohydrate (1.80 g, 45.0 mmol) was added to a solution oftert-butyl 4-cyclopropyl-3-oxopropionate (5.53 g, 30.0 mmol) in ethanol(50 ml) at 0° C., and the mixture was stirred at room temperature for 4hours. After completion of the reaction, a precipitated solid wasfiltered and washed with diethyl ether, to give a white solid of5-cyclopropyl-3-hydroxypyrazole (2.08 g, yield: 55.9%). mp: 213-215° C.;¹H-NMR (DMSO-d₆, DMSO, ppm): δ 0.55-0.65 (m, 2H), 0.75-0.95 (m, 2H),1.65-1.85 (m, 1H), 5.12 (s, 1H). (Amino proton and hydroxy proton werenot assigned.)

Referential Example 11

Hydrazine monohydrate (0.80 g, 20 mmol) was added to a solution ofmethyl 4-chlorobenzoylacetate (3.19 g, 15.0 mmol) in ethanol (40 ml) at0° C., and the mixture was stirred at room temperature for 2 days. Aftercompletion of the reaction, a precipitated solid was filtered and washedwith diethyl ether, to give a white solid of5-(4-chlorophenyl)-3-hydroxypyrazole (2.02 g, yield: 55.1%). mp:240-241° C.; ¹H-NMR (DMSO-d₆, DMSO, ppm): δ 5.92 (s, 1H), 7.47 (d, J=8.5Hz, 2H), 7.70 (d, J=8.5 Hz, 2H), 9.30-10.60 (br s, 1H), 11.60-12.70 (brs, 1H).

Referential Example 12

Hydrazine monohydrate (6.7 g, 210 mmol) was added to a solution ofdimethyl acetylenedicarboxylate (24.7 g, 175 mmol) in toluene (90 ml) at0° C., and the thus-obtained mixture was gradually temperature-increasedup to room temperature, stirred for 2 hours and further stirred underheating at 130° C. for 4 hours. After completion of the reaction, aprecipitated solid was filtered and washed with diethyl ether, to give awhite solid of methyl 3-hydroxypyrazole-5-carboxylate (18.2 g, yield:73.8%). mp: 229-231° C.; ¹H-NMR (DMSO-d₆, DMSO, ppm): δ 3.79 (s, 3H),5.91 (s, 1H), 10.10-10.45 (br s, 1H). (Hydroxy proton was not assigned.)

Referential Example 13

Sulfuryl chloride (4.86 g, 36 mmol) was added to a solution of3-hydroxy-5-methylpyrazole (2.94 g, 30.0 mmol) in acetic acid (25 ml),and the mixture was stirred at room temperature for 6 hours. Aftercompletion of the reaction, the reaction mixture was poured into icewater, and a precipitated solid was filtered and washed with water, togive a yellowish solid of 4-chloro-3-hydroxy-5-methylpyrazole (1.48 g,yield: 37.2%). mp: 235-238° C. (dec.); ¹H-NMR (CDCl₃, TMS, ppm): δ 2.10(s, 3H), 8.75-9.15 (m, 2H).

Referential Example 14

Potassium carbonate (3.52 g, 25.5 mmol) was added to a solution of3-hydroxy-5-methylpyrazole (5.00 g, 51.0 mmol) in DMF (80 ml). Then,allylisocyanate (4.51 ml, 51.0 mmol) was added, and the mixture wasstirred at room temperature for 6 hours. After completion of thereaction, the reaction mixture was poured into 1N hydrochloric acid andextracted with ethyl acetate (50 ml×2). An organic layer was washed withwater (50 ml×3), dried over anhydrous magnesium sulfate and thenfiltered to remove a desiccant, and the solvent was distilled off from afiltrate under reduced pressure. The resultant crude product waspurified with a silica gel column (ethyl acetate/hexane=1/3), to give awhite solid of N-allyl-3-hydroxy-5-methylpyrazole-1-carboxamide (4.72 g,yield: 51.1%). mp: 80-83° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.55 (d, J=0.8Hz, 3H), 3.97 (dddt, J=1.6, 1.6, 5.8 and 5.8 Hz, 2H), 5.19 (ddt, J=1.6,2.7 and 10.3 Hz, 1H), 5.28 (ddt, J=1.6, 2.7 and 17.2 Hz, 1H), 5.63 (d,J=0.8 Hz, 1H), 5.90 (ddt, J=5.8, 10.3 and 17.2 Hz, 1H), 6.70 (m, 1H).(Hydroxy proton was not assigned.)

Referential Example 15

Reaction of 3-hydroxy-5-methylpyrazole with phenyl isocyanate wascarried out in the same manner as in Referential Example 14, to give awhite solid of N-phenyl-3-hydroxy-5-methylpyrazol-1-carboxamide (yield:18.9%). mp: 232-234° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.62 (d, J=0.8 Hz,3H), 5.72 (d, J=0.8 Hz, 1H), 7.11-7.17 (m, 1H), 7.33-7.39 (m, 2H),7.53-7.57 (m, 2H), 8.64 (br s, 1H). (Hydroxy proton was not assigned.)

Example 1

Potassium carbonate (0.5 g, 3.6 mmol) and 4-fluoronitrobenzene (1.6 g,1.0 mmol) were added to a solution of 3-hydroxy-5-methylpyrazole (0.33g, 3.4 mmol) in DMF (50 ml) at room temperature, and further, themixture was stirred at room temperature for 8 hours. After completion ofthe reaction, the reaction mixture was poured into 2N hydrochloric acid(100 ml) and extracted with ethyl acetate (30 ml×3). An organic layerwas washed with water, dried over anhydrous magnesium sulfate andfiltered to remove a desiccant, and the solvent was distilled off fromthe filtrate under reduced pressure. The resultant crude product waspurified with a silica gel column (ethyl acetate/hexane=1/7→1/3), togive a white solid of 5-methyl-3-(4-nitrophenyloxy)pyrazole (0.4 g,yield: 63.3%) mp: 124-125° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.33 (s, 3H),5.75 (s, 1H), 7.20 (dd, J=2.2 and 7.1 Hz, 2H), 8.22 (dd, J=2.2 and 7.1Hz, 2H), 9.30-9.90 (br s, 1H).

Example 2

Potassium carbonate (3.19 g, 23.1 mmol) and 2,5-difluoronitrobenzene(7.34 g, 46.1 mmol) were added to a solution of3-hydroxy-5-methylpyrazole (4.52 g, 46.1 mmol) in DMF (80 ml) at roomtemperature, and the mixture was stirred at room temperature overnight.After completion of the reaction, the reaction mixture was poured into1N hydrochloric acid (100 ml) and extracted with ethyl acetate (100ml×2). An organic layer was washed with water (100 ml×2), dried overanhydrous magnesium sulfate and filtered to remove magnesium sulfate,and the solvent was distilled off from the filtrate under reducedpressure. The resultant crude product was purified with a silica gelcolumn (ethyl acetate/hexane=1/3), to give a yellow solid of3-(4-fluoro-2-nitrophenyloxy)-5-methylpyrazole (5.33 g, yield: 48.8%).mp: 81-84° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.28 (d, J=0.5 Hz, 3H), 5.71(d, J=0.5 Hz, 1H), 7.26-7.38 (m, 2H), 7.69 (dd, J=2.8 and 7.9 Hz, 1H),9.33 (br s, 1H).

Example 3

Potassium carbonate (2.23 g, 16.1 mmol) was added to a solution of3-hydroxy-5-methylpyrazole (3.16 g, 32.2 mmol) and5-fluoro-2-nitrotoluene (5.00 g, 32.2 mmol) in DMF (50 ml), and themixture was stirred at 70° C. for 3 hours. After completion of thereaction, a reaction mixture was poured into 2N hydrochloric acid (50ml) and extracted with ethyl acetate (30 ml×2). An organic layer waswashed with water (50 ml×3), dried over anhydrous magnesium sulfate andfiltered to remove a desiccant, and the solvent was distilled off fromthe filtrate under reduced pressure. The resultant crude product waspurified with a silica gel column (ethyl acetate/hexane=1/3), to give ayellowish solid of 5-methyl-3-(4-nitro-3-methylphenyloxy)pyrazole (2.51g, yield: 27.8%). mp: 114-117° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.30 (d,J=0.5 Hz, 3H), 2.61 (s, 3H), 5.72 (d, J=0.5 Hz, 1H), 6.98-7.04 (m, 2H),8.05 (d, J=9.8 Hz, 1H), 10.12 (br s, 1H).

Example 4

Reaction of 3-hydroxy-5-methylpyrazole with 5-chloro-2-nitroanisole wascarried out in the same manner as Example 3, to give a yellow viscoussubstance of 5-methyl-3-(3-methoxy-4-nitrophenyloxy)pyrazole (yield:13.2%). ¹H-NMR (CDCl₃, TMS, ppm): δ 2.34 (s, 3H), 3.93 (s, 3H), 5.74 (s,1H), 6.70 (dd, J=2.4 and 9.1 Hz, 1H), 6.85 (d, J=2.4 Hz, 1H), 7.95 (d,J=9.1 Hz, 1H), 9.45 (br s, 1H).

Example 5

Potassium carbonate (9.12 g, 66.0 mmol) was added to a solution of3-hydroxy-5-methylpyrazole (5.88 g, 60.0 mmol) and4-fluoro-3-nitrobenzotrifluoride (12.6 g, 60.0 mmol) in DMF (120 ml),and the mixture was stirred at 50° C. for 4 hours. After completion ofthe reaction, the reaction mixture was poured into 2N hydrochloric acid(200 ml) and extracted with ethyl acetate (70 ml×3). An organic layerwas washed with water, dried over anhydrous magnesium sulfate andfiltered to remove a desiccant, and the solvent was distilled off fromthe filtrate under reduced pressure. The resultant crude product waspurified with a silica gel column (ethyl acetate/hexane=1/3), to give ayellow solid of 5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole(12.1 g, yield: 69.0%). mp: 89-91° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.28(s, 3H), 5.77 (s, 1H), 7.40 (d, J=8.8 Hz, 1H), 7.76 (dd, J=2.0 and 8.8Hz, 1H), 8.21 (d, J=2.0 Hz, 1H), 10.10-11.05 (br s, 1H).

Examples 6-9

Reactions of 4-fluoro-3-nitrobenzotrifluoride with 3-hydroxypyrazolederivative (Example 6: 3-hydroxy-5-trifluoromethylpyrazole, Example 7:5-ethyl-3-hydroxypyrazole, Example 8: 4,5-dimethyl-3-hydroxypyrazole,Example 9: 4-ethyl-3-hydroxy-5-methylpyrazole) were carried out in thesame manner as in Example 5, to give corresponding 3-aryloxypyrazolederivatives. Products/forms/yields/melting points/NMR spectra aredescribed below.

Example 6

3-(2-nitro-4-trifluoromethylphenyloxy)-5-trifluoromethylpyrazole/yellowviscous substance/yield: 28.7%/¹H-NMR (CDCl₃, TMS, ppm): δ 6.35 (s, 1H),7.48 (d, J=8.5 Hz, 1H), 7.85 (dd, J=2.0 and 8.8 Hz, 1H), 8.27 (m, 1H),10.10-10.90 (br s, 1H).

Example 7

5-ethyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole/yellow viscoussubstance/yield: 77.0%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.27 (t, J=7.6 Hz,3H), 2.67 (dq, J=0.4 and 7.6 Hz, 2H), 5.81 (s, 1H), 7.44 (d, J=8.8 Hz,1H), 7.77 (dd, J=1.9 and 8.8 Hz, 1H), 8.22 (d, J=1.9 Hz, 1H). (Aminoproton was not assigned.)

Example 8

4,5-dimethyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole/yellowishsolid/yield: 50.8%/mp: 92-95° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.89 (s,3H), 2.23 (s, 3H), 7.38 (d, J=8.8 Hz, 1H), 7.74 (dd, J=1.9 and 8.8 Hz,1H), 8.22 (d, J=1.9 Hz, 1H), 8.90-10.35 (br s, 1H).

Example 9

4-ethyl-5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole/yellowsolid/yield: 49.8%/mp: 92-93° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.10 (t,J=7.6 Hz, 3H), 2.24 (s, 3H), 2.36 (q, J=7.6 Hz, 2H), 7.42 (d, J=8.8 Hz,1H), 7.74 (dd, J=2.0 and 8.8 Hz, 1H), 8.22 (d, J=2.0 Hz, 1H), 9.10-9.75(brs, 1H).

Example 10

Potassium carbonate (7.60 g, 55.0 mmol) was added to a solution of3-hydroxy-5-methylpyrazole (4.90 g, 50.0 mmol) and2-fluoro-5-nitrobenzotrifluoride (10.5 g, 50.0 mmol) in DMF (50 ml), andthe mixture was stirred under heating at 60° C. for 4 hours. Aftercompletion of the reaction, the reaction mixture was poured into 2Nhydrochloric acid (100 ml) and extracted with ethyl acetate (50 ml×3).An organic layer was washed with water, dried over anhydrous magnesiumsulfate and filtered to remove a desiccant, and the solvent wasdistilled off from the filtrate under reduced pressure. The resultantcrude product was purified with a silica gel column (ethylacetate/hexane=1/3), to give a yellowish viscous substance of5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole (8.70 g, yield:60.6%). ¹H-NMR (CDCl₃, TMS, ppm): δ 2.30 (d, J=0.5 Hz, 3H), 5.78 (d,J=0.5 Hz, 1H), 7.31 (d, J=9.2 Hz, 1H), 8.31 (dd, J=2.7 and 9.2 Hz, 1H),8.57 (d, J=2.7 Hz, 1H), 10.05-10.50 (br s, 1H).

Examples 11-13

Reactions of 2-fluoro-5-nitrobenzotrifluoride with 3-hydroxypyrazolederivative (Example 11: 5-ethyl-3-hydroxypyrazole, Example 12:4,5-dimethyl-3-hydroxypyrazole, Example 13:4-ethyl-3-hydroxy-5-methylpyrazole) were carried out in the same manneras in Example 10, to give corresponding 3-aryloxypyrazole derivatives.Products/forms/yields/melting points/NMR spectra are described below.

Example 11

5-ethyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole/yellow viscoussubstance/yield: 79.3%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.29 (t, J=7.6 Hz,3H), 2.69 (q, J=7.6 Hz, 2H), 5.82 (s, 1H), 7.38 (d, J=9.2 Hz, 1H), 8.35(dd, J=2.7 and 9.2 Hz, 1H), 8.57 (d, J=2.7 Hz, 1H), 9.45-10.15 (br s,1H).

Example 12

4,5-dimethyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole/yellowsolid/yield: 51.1%/mp: 97-99° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.84 (s,3H), 2.25 (s, 3H), 7.33 (d, J=9.2 Hz, 1H), 8.33 (dd, J=2.7 and 9.2 Hz,1H), 8.57 (d, J=2.7 Hz, 1H), 9.05˜10.20 (br s, 1H).

Example 13

4-ethyl-5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole/orangeviscous substance/yield: 50.8%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.05 (t,J=7.6 Hz, 3H), 2.26 (s, 3H), 2.31 (q, J=7.6 Hz, 2H), 7.36 (d, J=9.2 Hz,1H), 8.33 (dd, J=2.7 and 9.2 Hz, 1H), 8.57 (d, J=2.7 Hz, 1H). (Aminoproton was not assigned.)

Example 14

Potassium carbonate (3.52 g, 25.5 mmol) and 2,4-dichloronitrobenzene(9.79 g, 51.0 mmol) were added to a solution of3-hydroxy-5-methylpyrazole (5.00 g, 51.0 mmol) in DMF (130 ml) at roomtemperature, and the mixture was stirred at room temperature overnight.After completion of the reaction, the reaction mixture was poured into1N hydrochloric acid (200 ml) and extracted with ethyl acetate (100ml×3). An organic layer was washed with water (100 ml×3), dried overanhydrous magnesium sulfate and filtered to remove magnesium sulfate,and the solvent was distilled off from the filtrate under reducedpressure. The resultant crude product was purified with a silica gelcolumn (ethyl acetate/hexane=1/3), to give a yellow solid of3-(3-chloro-4-nitrophenyloxy)-5-methylpyrazole (6.33 g, yield: 48.9%)[mp: 91-93° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.30 (s, 3H), 5.74 (d, J=0.6Hz, 1H), 7.10 (dd, J=2.8 and 9.1 Hz, 1H), 7.25 (d, J=2.5 Hz, 1H), 7.97(d, J=9.1 Hz, 1H), 10.73 (br d, J=8.8 Hz, 1H)] and a yellow solid of3-(5-chloro-2-nitrophenyloxy)-5-methylpyrazole (2.31 g, yield: 17.9%)[mp: 87-90° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.27 (s, 3H), 5.73 (d, J=0.6Hz, 1H), 7.17 (dd, J=2.2 and 8.8 Hz, 1H), 7.26 (d, J=2.2 Hz, 1H), 7.91(d, J=8.8 Hz, 1H), 10.77 (br s, 1H)].

Example 15

Potassium carbonate (3.46 g, 25.0 mmol) and 2,4-difluoronitrobenzene(7.95 g, 50.0 mmol) were added to a solution of3-hydroxy-5-methylpyrazole (4.91 g, 50.0 mmol) in DMSO (80 ml) at roomtemperature, and the mixture was stirred at room temperature overnight.After completion of the reaction, the reaction mixture was poured into1N hydrochloric acid (100 ml) and extracted with ethyl acetate (100ml×2). An organic layer was washed with water (100 ml×2), dried overanhydrous magnesium sulfate and filtered to remove magnesium sulfate,and the solvent was distilled off from the filtrate under reducedpressure. The resultant crude product was purified with a silica gelcolumn (ethyl acetate/hexane=1/3), to give a yellow solid of3-(3-fluoro-4-nitrophenyloxy)-5-methylpyrazole (1.52 g, yield: 12.8%)[mp: 80-83° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.33 (d, J=0.5 Hz, 3H), 5.77(d, J=0.5 Hz, 1H), 6.96-7.03 (m, 2H), 8.06-8.13 (m, 1H), 10.03 (br s,1H)] and a yellow solid of3-(5-fluoro-2-nitrophenyloxy)-5-methylpyrazole (0.97 g, yield: 8.2%)[mp: 95-97° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.31 (s, 3H), 5.77 (s, 1H),6.90 (ddd, J=2.7, 5.8 and 9.1 Hz, 1H), 7.01 (dd, J=2.7 and 9.6 Hz, 1H),8.03 (dd, J=5.8 and 9.1 Hz, 1H), 9.86 (br s, 1H)].

Example 16

Potassium carbonate (2.49 g, 18.0 mmol) was added to a solution of3-hydroxy-5-methylpyrazole (1.47 g, 15.0 mmol) and5-fluoro-2-nitrobenzotrifluoride (3.14 g, 15.0 mmol) in DMF (20 ml), andthe mixture was stirred under heating at 70° C. for 3 hours. Aftercompletion of the reaction, the reaction mixture was poured into 2Nhydrochloric acid (40 ml) and extracted with ethyl acetate (30 ml×3). Anorganic layer was washed with water, dried over anhydrous magnesiumsulfate and filtered to remove a desiccant, and the solvent wasdistilled off from the filtrate under reduced pressure. The resultantcrude product was purified with a silica gel column (ethylacetate/hexane=1/3), to give a yellowish solid of5-methyl-3-(4-nitro-3-trifluoromethylphenyloxy)pyrazole (2.74 g, yield:63.6%). mp: 96-98° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.34 (s, 3H), 5.77(s, 1H), 7.40 (dd, J=2.6 and 8.9 Hz, 1H), 7.56 (d, J=2.6 Hz, 1H), 7.98(d, J=8.9 Hz, 1H), 9.20-10.15 (br s, 1H).

Example 17

Potassium carbonate (2.8 g, 20.0 mmol) was added to a solution of3-hydroxy-5-methylpyrazole (1.47 g, 15.0 mmol) and4-fluoro-3-trifluoromethylbenzonitrile (2.8 g, 15.0 mmol) in DMF (30ml), and the mixture was stirred under heating at 80° C. for 6 hours.After completion of the reaction, the reaction mixture was poured into2N hydrochloric acid (70 ml) and extracted with ethyl acetate (30 ml×3).An organic layer was washed with water, dried over anhydrous magnesiumsulfate and filtered to remove a desiccant, and the solvent wasdistilled off from the filtrate under reduced pressure. The resultantcrude product was purified with a silica gel column (ethylacetate/hexane=1/5), to give a yellowish solid of3-(4-cyano-2-trifluoromethylphenyloxy)-5-methylpyrazole (1.7 g, yield:42.4%). mp: 123-125° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.28 (d, J=0.5 Hz,3H), 5.75 (d, J=0.5 Hz, 1H), 7.30 (d, J=8.8 Hz, 1H), 7.75 (dd, J=2.0 and8.8 Hz, 1H), 7.96 (d, J=2.0 Hz, 1H), 9.60-11.60 (br s, 1H).

Example 18

Potassium carbonate (2.8 g, 20.0 mmol) was added to a solution of3-hydroxy-5-methylpyrazole (1.47 g, 15.0 mmol) and3,5-dichloro-4-fluorobenzotrifluoride (3.5 g, 15.0 mmol) in DMF (30 ml),and the mixture was stirred under heating at 60° C. for 6 hours. Aftercompletion of the reaction, the reaction mixture was poured into 2Nhydrochloric acid (70 ml) and extracted with ethyl acetate (30 ml×3). Anorganic layer was washed with water, dried over anhydrous magnesiumsulfate and filtered to remove a desiccant, and the solvent wasdistilled off from the filtrate under reduced pressure. The resultantcrude product was purified with a silica gel column (ethylacetate/hexane=1/10→1/7), to give a white solid of3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole (2.5 g,yield: 54.0%). mp: 153-155° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.27 (s,3H), 5.68 (s, 1H), 7.64 (s, 2H), 8.75-9.70 (br s, 1H).

Examples 19-29

Reactions of 3,5-dichloro-4-fluorobenzotrifluoride with3-hydroxypyrazole derivative (Example 19: 5-ethyl-3-hydroxypyrazole,Example 20: 3-hydroxy-5-isopropylpyrazole, Example 21:5-tert-butyl-3-hydroxypyrazole, Example 22:5-cyclopropyl-3-hydroxypyrazole, Example 23:4-ethyl-3-hydroxy-5-methylpyrazole, Example 24:3-hydroxy-5-(methoxymethyl)pyrazole, Example 25:ethyl(3-hydroxypyrazol-5-yl)acetate, Example 26: methyl3-hydroxypyrazole-5-carboxylate, Example 27:4,5-dimethyl-3-hydroxypyrazole, Example 28:4-ethyl-3-hydroxy-5-methylpyrazole, Example 29:5-(4-chlorophenyl)-3-hydroxypyrazole) were carried out in the samemanner as in Example 18, to give corresponding 3-aryloxypyrazolederivatives. Products/forms/yields/melting points/NMR spectra aredescribed below.

Example 19

3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-ethylpyrazole/whitesolid/yield: 35.7%/mp: 118-121° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.26 (t,J=7.5 Hz, 3H), 2.62 (q, J=7.5 Hz, 2H), 5.69 (s, 1H), 7.65 (s, 2H),8.90-9.30 (br s, 1H).

Example 20

3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-isopropylpyrazole/whitesolid/yield: 59.7%/mp: 98-101° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.26 (d,J=6.9 Hz, 6H), 2.90 (sep, J=6.9 Hz, 1H), 5.68 (d, J=0.2 Hz, 1H), 7.65(d, J=0.2 Hz, 2H), 9.06 (br s, 1H).

Example 21

5-tert-butyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)pyrazole/whitesolid/yield: 68.3%/mp: 170-172° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.30 (s,9H), 5.69 (s, 1H), 7.64 (s, 2H), 8.85-9.15 (m, 1H).

Example 22

5-cyclopropyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)pyrazole/whitesolid/yield: 16.8%/mp: 119-121° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.65-0.77(m, 2H), 0.90-1.05 (m, 2H), 1.70-1.85 (m, 1H), 5.54 (s, 1H), 7.65 (s,2H), 8.80-9.75 (br s, 1H).

Example 23

3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-(methoxymethyl)pyrazole/whitesolid/yield: 64.5%/mp: 141-143° C./¹H-NMR (CDCl₃, TMS, ppm): δ 3.41 (s,3H), 4.46 (s, 2H), 5.82 (s, 1H), 7.64 (s, 2H), 9.20˜9.65 (br s, 1H).

Example 24

methyl3-(2,6-dichloro-4-trifluoromethylphenyloxy)pyrazole-5-carboxylate/whitesolid/yield: 43.0%/mp: 114-116° C./¹H-NMR (CDCl₃, TMS, ppm): δ 3.93 (s,3H), 6.41 (s, 1H), 7.65 (d, J=0.4 Hz, 2H), 10.10 (br s, 1H).

Example 25

ethyl{3-(2,6-dichloro-4-trifluoromethylphenyloxy)pyrazol-5-yl}acetate/colorlessviscous substance/yield: 51.1%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.30 (t,J=7.2 Hz, 3H), 3.71 (s, 2H), 4.23 (q, J=7.2 Hz, 2H), 5.79 (s, 1H), 7.65(s, 2H). (Amino proton was not assigned.)

Example 26

3-(2,6-dichloro-4-trifluoromethylphenyloxy)-4,5-dimethylpyrazole/whitesolid/yield: 34.0%/mp: 220-223° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.90 (s,3H), 1.93 (s, 3H), 7.71 (s, 2H). (Amino proton was not assigned.)

Example 27

3-(2,6-dichloro-4-trifluoromethylphenyloxy)-4-ethyl-5-methylpyrazole/whitesolid/yield: 38.3%/mp: 215-218° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.10 (t,J=7.5 Hz, 3H), 1.93 (s, 3H), 2.34 (q, J=7.5 Hz, 2H), 7.69 (s, 2H),9.50-12.50 (br s, 1H).

Example 28

5-(4-chlorophenyl)-3-(2,6-dichloro-4-trifluoromethylphenyloxy)pyrazole/whitesolid/yield: 55.1%/mp: 181-183° C./¹H-NMR (CDCl₃, TMS, ppm): δ 5.99 (s,1H), 7.20-7.40 (m, 4H), 7.51 (s, 2H), 10.35-11.50 (br s, 1H).

Example 29

Potassium carbonate (1.66 g, 12 mmol) was added to a solution of3-hydroxy-5-methylpyrazole (2.45 g, 25.0 mmol) and3-chloro-4,5-difluorobenzotrifluoride (2.5 g, 25.0 mmol) in DMF (40 ml),and the mixture was stirred under heating at 70° C. for 4 hours. Aftercompletion of the reaction, the reaction mixture was poured into 2Nhydrochloric acid (100 ml) and extracted with ethyl acetate (50 ml×3).An organic layer was washed with water, dried over anhydrous magnesiumsulfate and filtered to remove a desiccant, and the solvent wasdistilled off from the filtrate under reduced pressure. The resultantcrude product was purified with a silica gel column (ethylacetate/hexane=1/5), to give a white solid of3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole (2.29g, yield: 33.8%). mp: 171-174° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.27 (s,3H), 5.71 (s, 1H), 7.37 (dd, J_(HF)=1.8 and 9.4 Hz, 1H), 7.54 (s, 1H),8.85-9.55 (br s, 1H).

Example 30

Sodium hydride (60% in oil, 0.2 g, 5.5 mmol) was added to a solution of3-hydroxy-5-methylpyrazole (0.49 g, 5.0 mmol) and3,5-dinitro-2-fluorobenzotrifluoride (1.35 g, 5.0 mmol) in DMF (10 ml),and the mixture was stirred under heating at 70° C. for 6 hours. Aftercompletion of the reaction, the reaction mixture was poured into 2Nhydrochloric acid (30 ml) and extracted with ethyl acetate (20 ml×3). Anorganic layer was washed with water, dried over anhydrous magnesiumsulfate and filtered to remove a desiccant, and the solvent wasdistilled off from the filtrate under reduced pressure. The resultantcrude product was purified with a silica gel column (ethylacetate/hexane=1/7), to give a yellowish solid of3-(2,4-dinitro-6-trifluoromethylphenyloxy)-5-methylpyrazole (0.58 g,yield: 34.9%). mp: 145-147° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.29 (s,3H), 5.84 (s, 1H), 8.82 (m, 2H), 9.01 (d, J=2.7 Hz, 1H).

Example 31

Sodium hydride (60% in oil, 0.44 g, 11.0 mmol) was added to a solutionof 3-hydroxy-5-methylpyrazole (0.98 g, 10.0 mmol) and3-chloro-4-fluoro-5-nitrobenzotrifluoride (1.5 g, 10.0 mmol) in DMF (30ml), and the mixture was stirred under heating at 60° C. for 7 hours.After completion of the reaction, the reaction mixture was poured into2N hydrochloric acid (80 ml) and extracted with ethyl acetate (30 ml×3).An organic layer was washed with water, dried over anhydrous magnesiumsulfate and filtered to remove a desiccant, and the solvent wasdistilled off from the filtrate under reduced pressure. The resultantcrude product was purified with a silica gel column (ethylacetate/hexane=1/7→1/3), to give a yellowish solid of3-(2-chloro-6-nitro-4-trifluoromethylphenyloxy)-5-methylpyrazole (1.8 g,yield: 56.6%). mp: 120-123° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.29 (s,3H), 5.79 (s, 1H), 7.98 (d, J=1.8 Hz, 1H), 8.17 (d, J=1.8 Hz, 1H),8.65-9.30 (br s, 1H).

Example 32

Sodium hydride (60% in oil, 0.2 g, 5.5 mmol) was added to a solution of3-hydroxy-5-methylpyrazole (0.49 g, 5.0 mmol) in DMF (10 ml) at 0° C.,and the mixture was stirred for 30 minutes while it was allowed to haveroom temperature gradually. Then, 2,3,5-trichloropyridine (0.9 g, 5.0mmol) was added, and the mixture was stirred under heating at 70° C. for2 days. After completion of the reaction, the reaction mixture waspoured into 2N hydrochloric acid (20 ml) and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/7→1/2), to give a white solid of3-(3,5-dichloropyridin-2-yloxy)-5-methylpyrazole (0.7 g, yield: 57.4%).mp: 109-111° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.32 (s, 3H), 5.86 (s, 1H),7.77 (d, J=2.3 Hz, 1H), 8.03 (d, J=2.3 Hz, 1H), 9.40-11.50 (br s, 1H).

Examples 34-35

Reactions of 3-hydroxy-5-methylpyrazole with pyridine derivative(Example 34: 2-chloro-6-methoxy-3-nitropyridine, Example 35:2-chloro-4-methyl-5-nitropyridine) were carried out in the same manneras in Example 33, to give corresponding 3-aryloxypyrazole derivatives.Products/forms/yields/melting points/NMR spectra are described below.

Example 33

5-methyl-3-(6-methoxy-3-nitropyridin-2-yloxy)pyrazole/yellowsolid/yield: 63.6%/mp: 133-136° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.32 (d,J=0.6 Hz, 3H), 3.80 (s, 3H), 5.90 (d, J=0.6 Hz, 1H), 6.51 (dd, J=1.7 and8.8 Hz, 1H), 8.39 (d, J=8.8 Hz, 1H), 10.90 (br s, 1H).

Example 34

5-methyl-3-(4-methyl-5-nitropyridin-2-yloxy)pyrazole/white solid/yield:39.8%/mp: 136-139° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.35 (d, J=0.5 Hz,3H), 2.67 (s, 3H), 5.91 (d, J=0.5 Hz, 1H), 6.94 (s, 1H), 8.93 (s, 1H),9.59 (br s, 1H).

Example 35

Potassium carbonate (7.60 g, 55.0 mmol) was added to a solution of3-hydroxy-5-methylpyrazole (4.90 g, 50.0 mmol) and2,3-dichloro-5-trifluoromethylpyridine (10.8 g, 50.0 mmol) in DMF (50ml) at room temperature, and the mixture was stirred under heating at60° C. for 4 hours. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid (100 ml) and extracted withethyl acetate (30 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column (ethylacetate/hexane=1/2), to give a white solid of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole (10.5 g,yield: 76.0%). mp: 93-95° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.32 (s, 3H),5.90 (s, 1H), 7.98 (d, J=2.0 Hz, 1H), 8.33 (m, 1H), 10.80-11.60 (br s,1H).

Examples 36-39

Reactions of 2,3-dichloro-5-trifluoromethylpyridine with3-hydroxypyrazole derivative (Example 36:3-hydroxy-5-trifluoromethylpyrazole, Example 37:5-ethyl-3-hydroxypyrazole, Example 38: 4,5-dimethylpyrazole-3-hydroxy,Example 39: 4-ethyl-3-hydroxy-5-methylpyrazole) were carried out in thesame manner as in Example 35, to give corresponding 3-aryloxypyrazolederivatives. Products/forms/yields/melting points/NMR spectra aredescribed below.

Example 36

3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-trifluoromethylpyrazole/colorlessviscous substance/yield: 41.5%/¹H-NMR (CDCl₃, TMS, ppm): δ 6.53 (s, 1H),8.05 (d, J=2.5 Hz, 1H), 8.38 (m, 1H), 10.90-11.65 (br s, 1H).

Example 37

3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-ethylpyrazole/whitesolid/yield: 85.2%/mp: 55-57° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.27 (t,J=7.5 Hz, 3H), 2.70 (q, J=7.5 Hz, 2H), 5.92 (s, 1H), 7.98 (d, J=2.5 Hz,1H), 8.34 (m, 1H), 10.15-10.70 (br s, 1H).

Example 38

3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-4,5-dimethylpyrazole/whitesolid/yield: 86.9%/mp: 102-103° C./¹H-NMR (DMSO-d₆, DMSO, ppm): δ 1.68(s, 3H), 2.17 (s, 3H), 8.53 (m, 1H), 8.57 (m, 1H), 12.05-12.25 (br s,1H).

Example 39

3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-4-ethyl-5-methylpyrazole/whitesolid/yield: 77.6%/mp: 74-75° C./¹H-NMR (DMSO-d₆, DMSO, ppm): δ 0.93 (t,J=7.6 Hz, 3H), 2.14 (q, J=7.6 Hz, 2H), 2.19 (s, 3H), 8.45-8.65 (m, 2H),12.00-12.30 (br s, 1H).

Example 40

Potassium hydrogencarbonate (0.15 g, 1.5 mmol) was added to a solutionof 3-(3-fluoro-4-nitrophenyloxy)-5-methylpyrazole (0.36 g, 1.5 mmol) inethanol (5 ml), and the mixture was refluxed under heating for 10 hours.After completion of the reaction, the reaction mixture was poured intowater (10 ml) and extracted with ethyl acetate (10 ml×2), dried overanhydrous magnesium sulfate and filtered to remove magnesium sulfate,and the solvent was distilled off from the filtrate under reducedpressure. The resultant crude product was purified with a silica gelcolumn (ethyl acetate/hexane=1/5), to give a yellow solid of3-(3-ethoxy-4-nitrophenyloxy)-5-methylpyrazole (0.17 g, yield: 42.3%).mp: 123-124° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.47 (t, J=7.0 Hz, 3H),2.33 (d, J=0.5 Hz, 3H), 4.13 (q, J=7.0 Hz, 2H), 5.73 (d, J=0.5 Hz, 1H),6.68 (dd, J=2.5 and 9.1 Hz, 1H), 6.81 (d, J=2.5 Hz, 1H), 7.91 (d, J=9.1Hz, 1H), 9.53 (br s, 1H).

Example 41

Reaction of 3-(5-fluoro-2-nitrophenyloxy)-5-methylpyrazole with ethanolwas carried out in the presence of potassium hydrogencarbonate in thesame manner as in Example 40, to give a yellow viscous substance of3-(5-ethoxy-2-nitrophenyloxy)-5-methylpyrazole (yield: 59.8%). ¹H-NMR(CDCl₃, TMS, ppm): δ 1.39 (t, J=7.0 Hz, 3H), 2.28 (s, 3H), 4.04 (q,J=7.0 Hz, 2H), 5.72 (s, 1H), 6.68 (dd, J=2.6 and 9.1 Hz, 1H), 6.73 (d,J=2.6 Hz, 1H), 8.04 (d, J=9.1 Hz, 1H), 9.62 (br s, 1H).

Example 42

A solution of 5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole(5.3 g, 18.5 mmol) in ethanol (200 ml) was placed in an autoclave, and10% palladium carbon (2.0 g) was added. An atmosphere in the autoclavewas fully replaced with hydrogen gas, and hydrogen gas was filled up to5 kg/cm². Then, the reaction solution was stirred at room temperaturefor 4 hours. After completion of the reaction, the catalyst wasseparated by filtration using Celite, and the solvent was distilled offfrom the filtrate under reduced pressure, to give a white solid of3-(4-amino-2-trifluoromethylphenyloxy)-5-methylpyrazole (3.6 g, yield:76.1%). mp: 143-145° C.; ¹H-NMR (DMSO-d₆, DMSO, ppm): δ 2.17 (s, 3H),5.33 (br s, 2H), 5.44 (s, 1H), 6.78 (dd, J=2.6 and 8.8 Hz, 1H), 6.88 (d,J=2.6 Hz, 1H), 6.95 (d, J=8.8 Hz, 1H), 11.80-11.95 (br s, 1H).

Examples 43-45

3-(Substituted phenyloxy)pyrazole derivative having a nitro group(Example 43: 5-methyl-3-(4-nitrophenyloxy)pyrazole, Example 44:3-(3-chloro-4-nitrophenyloxy)-5-methylpyrazole, Example 45:5-methyl-(4-nitro-3-trifluoromethylphenyloxy)pyrazole) was reduced in ahydrogen gas atmosphere in the same manner as in Example 42, to givecorresponding 3-(substituted phenyloxy)pyrazole derivative having anamino group. Products/forms/yields/melting points/NMR spectra aredescribed below.

Example 43

3-(4-aminophenyloxy)-5-methylpyrazole/brown solid/yield: 49.7%/mp:170-173° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.48-2.13 (br s, 2H), 2.23 (d,J=0.7 Hz, 3H), 5.47 (d, J=0.7 Hz, 1H), 6.64 (dd, J=2.2 and 7.1 Hz, 2H),6.95 (dd, J=2.2 and 7.1 Hz, 2H). (Amino proton was not assigned.)

Example 44

3-(4-amino-3-chlorophenyloxy)-5-methylpyrazole/brown viscoussubstance/yield: 27.4%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.26 (d, J=0.4 Hz,3H), 3.63 (br s, 2H), 5.60 (d, J=0.4 Hz, 1H), 6.70 (d, J=8.5 Hz, 1H),6.91 (dd, J=2.3 Hz and 8.5 Hz, 1H), 7.00 (d, J=2.3 Hz, 1H). (Aminoproton was not assigned.)

Example 45

3-(4-amino-3-trifluoromethylphenyloxy)-5-methylpyrazole/brown viscoussubstance/yield: 97.8%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.24 (s, 3H),3.85-4.25 (br s, 2H), 5.53 (s, 1H), 6.71 (d, J=8.8 Hz, 1H), 7.14 (dd,J=2.8 and 8.8 Hz, 1H), 7.25 (d, J=2.8 Hz, 1H). (Amino proton was notassigned.)

Example 46

Concentrated hydrochloric acid (3 ml) and water (6 ml) were added to3-(4-amino-3-trifluoromethylphenyloxy)-5-methylpyrazole, and the mixturewas cooled to 0° C. Then, a solution of sodium nitrite (0.54 g, 7.8mmol) in concentrated hydrochloric acid (2 ml) and water (2 ml) wasdropwise added, and the mixture was stirred at an ambient temperaturefor 1 hour. Then, hypophosphorous acid (2.57 g, 38.9 mmol) was added,and the mixture was stirred at room temperature overnight. Aftercompletion of the reaction, the reaction mixture was poured into 1Nsodium hydroxide (50 ml) and extracted with ethyl acetate (50 ml×2). Anorganic layer was washed with water (50 ml×2), dried over anhydrousmagnesium sulfate and filtered to remove a desiccant, and the solventwas distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/4), to give a yellow viscous substance of5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole (1.47 g, yield: 78.0%).¹H-NMR (CDCl₃, TMS, ppm): δ 2.2.3 (s, 3H), 5.63 (s, 1H), 7.27˜7.46 (m,4H), 10.91 (br s, 1H).

Examples 47-49

3-(Substituted phenyloxy)pyrazole derivative having an amino group(Example 47: 3-(4-aminophenyloxy)-5-methylpyrazole, Example 48:3-(4-amino-3-chlorophenyloxy)-5-methylpyrazole, Example 49:3-(4-amino-2-trifluoromethylphenyloxy)-5-methylpyrazole) was de-aminatedvia a diazonium salt in the same manner as in Example 46, to give3-(substituted phenyloxy)pyrazole derivative.Products/forms/yields/melting points/NMR spectra are described below.

Example 47

5-methyl-3-phenyloxypyrazole/brown viscous substance/yield: 72.2%/¹H-NMR(CDCl₃, TMS, ppm): δ 2.22 (s, 3H), 5.58 (s, 1H), 7.05-7.12 (m, 3H),7.27-7.35 (m, 2H). (Amino proton was not assigned.)

Example 48

3-(3-chlorophenyloxy)-5-methylpyrazole/yellow viscous substance/yield:22.4%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.23 (s, 3H), 5.62 (s, 1H), 6.95-7.13(m, 3H), 7.21 (d, J=8.1 Hz, 1H), 10.95 (br s, 1H).

Example 49

5-methyl-3-(2-trifluoromethylphenyloxy)pyrazole/yellowish viscoussubstance/yield: 75.8%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.20 (d, J=0.4 Hz,3H), 5.59 (d, J=0.4 Hz, 1H), 7.12-7.20 (m, 2H), 7.42-7.49 (m, 1H), 7.64(dd, J=0.9 and 7.7 Hz, 1H), 10.70-12.19 (br s, 1H).

Example 50

3-(4-Amino-3-trifluoromethylphenyloxy)-5-methylpyrazole (2.00 g, 7.8mmol) was added to a mixed solution of concentrated hydrochloric acid(2.1 ml) and acetone (20 ml) at room temperature, and the mixture wasstirred at room temperature for 20 minutes. After the mixture was cooledbelow 0° C., a solution of sodium nitrite (0.54 g, 7.8 mmol) in water (3ml) was dropwise added, and the mixture was stirred at an ambienttemperature for 30 minutes. Then, cuprous chloride (0.85 g, 8.6 mmol)was little by little added at 0° C., and the mixture was stirred at roomtemperature for 1 hour. After completion of the reaction, the reactionmixture was poured into 1N hydrochloric acid (50 ml) and extracted withethyl acetate (50 ml×2). An organic layer was washed with water (50ml×3), dried over anhydrous magnesium sulfate and filtered to remove adesiccant, and the solvent was distilled off from the filtrate underreduced pressure. The resultant crude product was purified with a silicagel column (ethyl acetate/hexane=1/3), to give a yellowish viscoussubstance of 3-(4-chloro-3-trifluoromethylphenyloxy)-5-methylpyrazole(2.12 g, yield: 98.7%). ¹H-NMR (CDCl₃, TMS, ppm): δ 2.25 (s, 3H), 5.64(s, 1H), 7.23 (dd, J=3.0 and 8.8 Hz, 1H), 7.31-7.46 (m, 2H), 10.56 (brs, 1H).

Example 51

A diazonium salt was prepared from3-(4-amino-2-trifluoromethylphenyloxy)-5-methylpyrazole and reacted withcuprous chloride in the same manner as in Example 50, to give ayellowish viscous substance of3-(4-chloro-2-trifluoromethylphenyloxy)-5-methylpyrazole (yield: 56.0%).¹H-NMR (CDCl₃, TMS, ppm): δ 2.24 (s, 3H), 5.63 (s, 1H), 7.16 (d, J=8.9Hz, 1H), 7.41 (dd, J=2.5 and 8.9 Hz, 1H), 7.61 (d, J=2.5 Hz, 1H), 10.93(br s, 1H).

Example 52

Sulfuryl chloride (0.48 g, 3.6 mmol) was added to a solution of3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole (0.93 g,3.0 mmol) in acetic acid (10 ml), and the mixture was stirred at roomtemperature for 4 hours. After completion of the reaction, the reactionmixture was poured into ice water and extracted with ethyl acetate (10ml×3). An organic layer was washed with water, dried over anhydrousmagnesium sulfate and filtered to remove a desiccant, and the solventwas distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid of4-chloro-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole(0.57 g, yield: 55.0%). mp: 156-158° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ2.28 (s, 3H), 7.65 (s, 2H), 8.75-9.15 (br s, 1H).

Example 53

Triethylamine (0.13 g, 1.3 mmol) was added to a solution of5-methyl-3-phenyloxypyrazole (0.20 g, 1.2 mmol) in ethyl acetate (5 ml),and the mixture cooled to 0° C. Then, ethyl isocyanate (0.09 g, 1.3mmol) was added, and the mixture was stirred for 30 minutes at anambient temperature. And, the mixture was stirred for 4 hours while itwas allowed to have room temperature gradually. After completion of thereaction, the reaction mixture was poured into 1N hydrochloric acid (10ml) and extracted with ethyl acetate (10 ml×2). An organic layer waswashed with water (10 ml×2), dried over anhydrous magnesium sulfate andfiltered to remove a desiccant, and the solvent was distilled off fromthe filtrate under reduced pressure. The resultant crude product waspurified with a silica gel column (ethyl acetate/hexane=1/15), to give ayellow viscous substance ofN-ethyl-5-methyl-3-phenyloxypyrazole-1-carboxamide (0.16 g, yield:56.4%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.22 (t, J=7.3 Hz, 3H), 2.58 (d,J=0.8 Hz, 3H), 3.38 (dq, J=1.3 and 7.3 Hz, 2H), 5.67 (q, J=0.8 Hz, 1H),6.99-7.07 (br s, 1H), 7.12-7.19 (m, 3H), 7.33-7.39 (m, 2H).

Example 54

Potassium carbonate (0.19 g, 1.5 mmol) and ethyl isocyanate (0.09 g, 1.3mmol) were added to a solution of 5-methyl-3-(4-nitrophenyloxy)pyrazole(0.29 g, 1.3 mmol) in ethyl acetate (15 ml), and the mixture was stirredat room temperature for 6 hours. After completion of the reaction, thereaction mixture was poured into 2N hydrochloric acid and extracted withdiethyl ether (10 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column (ethylacetate/hexane=1/20), to give a white solid ofN-ethyl-5-methyl-3-(4-nitrophenyloxy)pyrazole-1-carboxamide (0.38 g,yield: 99.2%). mp: 105-107° C., ¹H-NMR (CDCl₃, TMS, ppm): δ 1.24 (t,J=7.3 Hz, 3H), 2.64 (d, J=0.7 Hz, 3H), 3.40 (dq, J=5.9 and 7.2 Hz, 2H),5.83 (q, J=0.7 Hz, 1H), 6.75 (m, 1H), 7.20-7.30 (m, 2H), 8.26 (dd, J=2.2and 7.0 Hz, 2H).

Example 55

Triethylamine (0.19 g, 1.4 mmol) and phenyl isocyanate (0.17 g, 1.4mmol) were added to a solution of5-methyl-3-(2-trifluoromethylphenyloxy)pyrazole (0.30 g, 1.2 mmol) inethyl acetate (5 ml) at 0° C., and the mixture was allowed to have roomtemperature gradually and stirred for 6 hours. After completion of thereaction, the reaction mixture was poured into 1N hydrochloric acid (10ml) and extracted with ethyl acetate (10 ml×2). An organic layer waswashed with water (10 ml×2), dried over anhydrous magnesium sulfate andfiltered to remove a desiccant, and the solvent was distilled off fromthe filtrate under reduced pressure. The resultant crude product waspurified with a silica gel column (ethyl acetate/hexane=1/15), to givean orange solid ofN-phenyl-5-methyl-3-(2-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.39 g, yield: 87.5%). mp: 87-89° C., ¹H-NMR (CDCl₃, TMS, ppm): δ 2.65(d, J=0.7 Hz, 3H), 5.78 (d, J=0.7 Hz, 1H), 7.14 (ddd, J=1.2, 2.3 and 7.3Hz, 1H), 7.28-7.38 (m, 4H), 7.51-7.60 (m, 3H), 7.69-7.73 (m, 1H), 8.90(br s, 1H).

Example 56

Triethylamine (0.17 g, 1.7 mmol) and isopropyl isocyanate (0.14 g, 1.7mmol) were added to a solution of5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole (0.36 g, 1.5 mmol) inethyl acetate (5 ml), and the mixture was stirred at room temperaturefor 6 hours. After completion of the reaction, the reaction mixture waspoured into 1N hydrochloric acid (10 ml) and extracted with ethylacetate (10 ml×3). An organic layer was washed with water (10 ml×2),dried over anhydrous magnesium sulfate and filtered to remove adesiccant, and the solvent was distilled off from the filtrate underreduced pressure. The resultant crude product was purified with a silicagel column (ethyl acetate/hexane=1/15), to give a colorless viscoussubstance ofN-isopropyl-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.15 g, yield: 30.6%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.25 (d, J=6.6 Hz,6H), 2.60 (d, J=0.6 Hz, 3H), 4.05 (sep, J=6.6 and 6.6 Hz, 1H), 5.71 (q,J=0.6 Hz, 1H), 6.81 (br d, J=6.6 Hz, 1H), 7.30-7.35 (m, 1H), 7.40-7.52(m, 3H).

Examples 57-82

Reactions of 5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole andisocyanates (Example 57: ethyl isocyanate, Example 58: tert-butylisocyanate, Example 59: hexyl isocyanate, Example 60: cyclohexylisocyanate, Example 61: allyl isocyanate, Example 62: 2-chloroethylisocyanate, Example 63: ethyl isocyanatoacetate, Example 64: phenylisocyanate, Example 65: 2-chlorophenyl isocyanate, Example 66:3-chlorophenyl isocyanate, Example 67: 3-methylphenyl isocyanate,Example 68: 3-nitrophenyl isocyanate, Example 69: 4-chlorophenylisocyanate, Example 70: 4-fluorophenyl isocyanate, Example 71:4-trifluoromethylphenyl isocyanate, Example 72: 2,4-dichlorophenylisocyanate, Example 73: 2,4-difluorophenyl isocyanate, Example 74:3,4-dichlorophenyl isocyanate, Example 75: 2,6-dichlorophenylisocyanate, Example 76: 4-chloro-2-methylphenyl isocyanate, Example 77:2-methyl-4-nitrophenyl isocyanate, Example 78: 2-chloro-6-methylphenylisocyanate, Example 79: 2,3,4-trifluorophenyl isocyanate, Example 80:4-chloro-5-cyclopentyloxy-2-fluorophenyl isocyanate, Example 81: benzylisocyanate, Example 82: α-phenethyl isocyanate) were carried out inethyl acetate in the presence of potassium carbonate in the same manneras in Example 56, to give corresponding N-substituted carboxamides.Products/forms/yields/melting points/NMR spectra are described below.

Example 57

N-ethyl-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowviscous substance/yield: 63.8%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.23 (t,J=7.3 Hz, 3H), 2.60 (d, J=0.8 Hz, 3H), 3.39 (dq, J=6.0 and 7.3 Hz, 2H),5.73 (q, J=0.8 Hz, 1H), 6.80-7.05 (m, 1H), 7.25-7.55 (m, 4H).

Example 58

N-tert-butyl-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/colorlessviscous substance/yield: 11.7%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.43 (s, 9H),2.59 (d, J=0.6 Hz, 3H), 5.69 (q, J=0.6 Hz, 1H), 6.95 (br s, 1H),7.29-7.34 (m, 1H), 7.45-7.51 (m, 3H).

Example 59

N-hexyl-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowviscous substance/yield: 53.1%/¹H-NMR (CDCl₃, TMS, ppm): δ 0.86-0.91 (m,3H), 1.26-1.41 (m, 6H), 1.52-1.64 (m, 2H), 2.60 (d, J=0.7 Hz, 3H),3.29-3.37 (m, 2H), 5.73 (q, J=0.7 Hz, 1H), 6.95 (br s, 1H), 7.32-7.51(m, 4H).

Example 60

N-cyclohexyl-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowviscous substance/yield: 26.7%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.11-1.47 (m,5H), 1.59-1.80 (m, 3H), 1.94-2.04 (m, 2H), 2.60 (d, J=0.7 Hz, 3H),3.65-3.80 (m, 1H), 5.71 (q, J=0.7 Hz, 1H), 6.88 (br d, J=7.5 Hz, 1H),7.30-7.35 (m, 1H), 7.40-7.51 (m, 3H).

Example 61

N-allyl-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/colorlessviscous substance/yield: 83.9%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.61 (d,J=0.8 Hz, 3H), 3.97 (tt, J=1.5 and 5.8 Hz, 2H), 5.15-5.30 (m, 2H), 5.75(q, J=0.8 Hz, 1H), 5.80-5.97 (m, 1H), 7.06 (br s, 1H), 7.32-7.36 (m,1H), 7.40-7.52 (m, 3H).

Example 62

N-(2-chloroethyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/colorlessviscous substance/yield: 71.0%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.60 (d,J=0.7 Hz, 3H), 3.67-3.70 (m, 4H), 5.76 (q, J=0.7 Hz, 1H), 7.30-7.38 (m,2H), 7.41-7.49 (m, 3H).

Example 63

ethyl[{3-(3-trifluoromethylphenyloxy)-5-methylpyrazol-1-yl}carbonylamino]acetate/whitesolid/yield: 73.7%/mp: 66-68° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.29 (t,J=7.2 Hz, 3H), 2.60 (d, J=0.8 Hz, 3H), 4.10 (d, J=5.8 Hz, 2H), 4.24 (q,J=7.2 Hz, 2H), 5.76 (q, J=0.8 Hz, 1H), 7.31-7.49 (m, 5H).

Example 64

N-phenyl-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowishsolid/yield: 94.0%/mp: 53-54° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.67 (d,J=0.8 Hz, 3H), 5.80 (q, J=0.8 Hz, 1H), 7.15 (ddt, J=1.1, 7.4 and 7.4 Hz,1H), 7.30-7.60 (m, 8H), 8.89 (br s, 1H).

Example 65

N-2-chlorophenyl-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowishsolid/yield: 70.7%/mp: 84-86° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.67 (d,J=0.7 Hz, 3H), 5.85 (q, J=0.7 Hz, 1H), 7.06 (ddt, J=1.5, 7.8 and 7.8 Hz,1H), 7.20-7.60 (m, 6H), 8.30 (dd, J=1.5 and 8.3 Hz, 1H), 9.56 (br s,1H).

Example 66

N-3-chlorophenyl-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowviscous substance/yield: 94.0%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.66 (d,J=0.9 Hz, 3H), 5.81 (q, J=0.9 Hz, 1H), 7.11 (ddd, J=1.3, 1.9 and 7.5 Hz,1H), 7.23-7.39 (m, 3H), 7.45-7.55 (m, 3H), 7.70 (t, J=1.9 Hz, 1H), 8.91(br s, 1H).

Example 67

N-(3-methylphenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowsolid/yield: 92.2%/mp: 47-49° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.36 (s,3H), 2.66 (d, J=0.7 Hz, 3H), 5.80 (q, J=0.7 Hz, 1H), 6.96 (dd, J=0.4 and7.3 Hz, 1H), 7.20-7.29 (m, 2H), 7.29-7.41 (m, 2H), 7.43-7.54 (m, 3H),8.84 (br s, 1H).

Example 68

N-(3-nitrophenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowsolid/yield: 80.5%/mp: 83-86° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.68 (d,J=0.7 Hz, 3H), 5.84 (q, J=0.7 Hz, 1H), 7.36-7.40 (m, 1H), 7.46-7.57 (m,4H), 7.83 (ddd, J=0.9, 2.2 and 8.2 Hz, 1H), 7.99 (ddd, J=0.9, 2.2 and8.2 Hz, 1H), 8.52 (dd, J=2.2 and 2.2 Hz, 1H), 9.11 (br s, 1H).

Example 69

N-(4-chlorophenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/whitesolid/yield: 88.9%/mp: 73-74° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.66 (d,J=0.8 Hz, 3H), 5.81 (q, J=0.8 Hz, 1H), 7.29-7.39 (m, 3H), 7.44-7.55 (m,5H), 8.88 (br s, 1H).

Example 70

N-(4-fluorophenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowsolid/yield: 77.0%/mp: 70-72° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.66 (d,J=0.8 Hz, 3H), 5.80 (q, J=0.8 Hz, 1H), 7.00˜7.09 (m, 2H), 7.35-7.39 (m,1H), 7.43-7.54 (m, 5H), 8.84 (br s, 1H).

Example 71

N-(4-trifluoromethylphenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowishsolid/yield: 90.8%/mp: 82-84° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.67 (d,J=0.9 Hz, 3H), 5.83 (q, J=0.9 Hz, 1H), 7.32-7.40 (m, 1H), 7.45-7.56 (m,3H), 7.64 (dd, J=8.9 and 15.6 Hz, 4H), 9.06 (br s, 1H).

Example 72

N-(2,4-dichlorophenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/colorlessviscous substance/yield: 63.7%/mp: 113-114° C./¹H-NMR (CDCl₃, TMS, ppm):δ 2.66 (d, J=0.6 Hz, 3H), 5.85 (1H), 7.25-7.30 (m, 1H), 7.39-7.56 (m,5H), 8.27 (d, J=8.8 Hz, 1H), 9.52 (br s, 1H).

Example 73

N-(2,4-difluorophenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowishsolid/yield: 45.3%/mp: 84-85° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.66 (d,J=0.8 Hz, 3H), 5.83 (q, J=0.8 Hz, 1H), 6.80-6.95 (m, 2H), 7.35-7.60 (m,4H), 8.05-8.20 (m, 1H), 9.00 (br s, 1H).

Example 74

N-(3,4-dichlorophenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/whitesolid/yield: 85.2%/mp: 97-99° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.65 (d,J=0.7 Hz, 3H), 5.82 (q, J=0.7 Hz, 1H), 7.32 (dd, J=2.5 and 8.8 Hz, 1H),7.35-7.56 (m, 5H), 7.81 (d, J=2.4 Hz, 1H), 8.90 (br s, 1H).

Example 75

N-(2,6-dichlorophenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowishviscous substance/yield: 50.2%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.64 (d,J=0.8 Hz, 3H), 5.84 (q, J=0.8 Hz, 1H), 7.21 (dd, J=7.5 and 8.8 Hz, 1H),7.39-7.53 (m, 6H), 8.57 (br s, 1H).

Example 76

N-(4-chloro-2-methylphenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/whitesolid/yield: 83.7%/mp: 95-96° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.21 (s,3H), 2.65 (d, J=0.8 Hz, 3H), 5.83 (q, J=0.8 Hz, 1H), 7.17-7.23 (m, 2H),7.37-7.54 (m, 4H), 7.91 (d, J=8.4 Hz, 1H), 8.82 (br s, 1H).

Example 77

N-(2-methyl-4-nitrophenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowishsolid/yield: 16.7%/mp: 165-166° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.29 (s,3H), 2.68 (d, J=0.8 Hz, 3H), 5.88 (q, J=0.8 Hz, 1H), 7.39-7.43 (m, 1H),7.47-7.57 (m, 3H), 8.08-8.16 (m, 2H), 8.37 (d, J=9.0 Hz, 1H), 9.24 (brs, 1H).

Example 78

N-(2-chloro-6-methylphenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/whitesolid/yield: 66.1%/mp: 55-58° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.36 (s,3H), 2.64 (d, J=0.8 Hz, 3H), 5.83 (q, J=0.8 Hz, 1H), 7.12-7.20 (m, 2H),7.30 (dd, J=2.9 and 6.5 Hz, 1H), 7.39-7.54 (m, 4H), 8.52 (br s, 1H).

Example 79

N-(2,3,4-trifluorophenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/whitesolid/yield: 73.4%/mp: 102-104° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.65 (d,J=0.8 Hz, 3H), 5.84 (q, J=0.8 Hz, 1H), 6.93-7.05 (m, 1H), 7.38-7.42 (m,1H), 7.45-7.56 (m, 3H), 7.85˜7.92 (m, 1H), 9.30 (br s, 1H).

Example 80

N-(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/whitesolid/yield: 52.0%/mp: 81-83° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.55-1.70(m, 2H), 1.75-2.00 (m, 6H), 2.66 (d, J=0.8 Hz, 3H), 4.75-4.90 (m, 1H),5.82 (q, J=0.8 Hz, 1H), 7.14 (d, J=10.2 Hz, 1H), 7.35-7.55 (m, 4H), 7.97(d, J=7.3 Hz, 1H), 9.00-9.20 (m, 1H).

Example 81

N-benzyl-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/colorlessviscous substance/yield: 56.8%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.62 (d,J=0.8 Hz, 3H), 4.53 (d, J=6.0 Hz, 2H), 5.74 (q, J=0.8 Hz, 1H), 7.20˜7.50(m, 10H).

Example 82

N-α-phenethyl-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/colorlessviscous substance/yield: 63.7%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.57 (d,J=6.9 Hz, 3H), 2.58 (s, 3H), 5.06 (dq, J=7.1 and 7.1 Hz, 1H), 5.71 (s,1H), 7.26-7.36 (m, 7H), 7.43-7.51 (m, 3H).

Example 83

Triethylamine (0.13 g, 1.3 mmol) and phenyl isocyanate (0.15 g, 1.3mmol) were added to a solution of 3-(3-chlorophenyloxy)-5-methylpyrazole(0.25 g, 1.2 mmol) in ethyl acetate (5 ml) at 0° C., and while themixture was allowed to have room temperature gradually, it was stirredfor 6 hours. After completion of the reaction, the reaction mixture waspoured into 1N hydrochloric acid (10 ml) and extracted with ethylacetate (10 ml×2). An organic layer was washed with water (10 ml×2),dried over anhydrous magnesium sulfate and filtered to remove adesiccant, and the solvent was distilled off from the filtrate underreduced pressure. The resultant crude product was purified with a silicagel column (ethyl acetate/hexane=1/15), to give a yellow viscoussubstance ofN-phenyl-3-(3-chlorophenyloxy)-5-methylpyrazole-1-carboxamide (0.34 g,yield: 84.5%). ¹H-NMR (CDCl₃, TMS, ppm): δ 2.66 (d, J=0.8 Hz, 3H), 5.78(q, J=0.8 Hz, 1H), 7.05-7.11 (m, 1H), 7.14-7.21 (m, 3H), 7.28-7.39 (m,3H), 7.52-7.56 (m, 2H), 8.91 (br s, 1H).

Example 84

Triethylamine (0.17 g, 1.65 mmol) and ethyl isocyanate (0.31 g, 2.2mmol) were added to a solution of3-(4-chloro-2-trifluoromethylphenyloxy)-5-methylpyrazole (0.55 g, 2.0mmol) in ethyl acetate (5 ml), and the mixture was stirred at roomtemperature for 6 hours. After completion of the reaction, the reactionmixture was poured into 1N hydrochloric acid (10 ml) and extracted withethyl acetate (10 ml×3). An organic layer was washed with water (10ml×2), dried over anhydrous magnesium sulfate and filtered to remove adesiccant, and the solvent was distilled off from the filtrate underreduced pressure. The resultant crude product was purified with a silicagel column (ethyl acetate/hexane=1/15), to give a colorless viscoussubstance ofN-ethyl-3-(4-chloro-2-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.53 g, yield: 75.9%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.22 (t, J=7.3 Hz,3H), 2.59 (d, J=0.7 Hz, 3H), 3.37 (q, J=7.3 Hz, 2H), 5.73 (q, J=0.7 Hz,1H), 6.91 (br s, 1H), 7.22 (d, J=8.8 Hz, 1H), 7.49 (dd, J=2.5 and 8.8Hz, 1H), 7.65 (d, J=2.5 Hz, 1H).

Example 85

Triethylamine (0.32 g, 3.2 mmol) and ethyl isocyanate (0.23 g, 3.2 mmol)were added to a solution of3-(4-fluoro-2-nitrophenyloxy)-5-methylpyrazole (0.69 g, 2.9 mmol) inethyl acetate (10 ml) at 0° C., and the mixture was allowed to have roomtemperature gradually and stirred for 5 hours. After completion of thereaction, the reaction mixture was poured into 1N hydrochloric acid (10ml) and extracted with ethyl acetate (10 ml×2). An organic layer waswashed with water (10 ml×2), dried over anhydrous magnesium sulfate andfiltered to remove a desiccant, and the solvent was distilled off fromthe filtrate under reduced pressure. The resultant crude product waspurified with a silica gel column (ethyl acetate/hexane=1/15), to give ayellow solid ofN-ethyl-3-(4-fluoro-2-nitrophenyloxy)-5-methylpyrazole-1-carboxamide(0.72 g, yield: 79.7%). mp: 81-84° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.20(t, J=7.2 Hz, 3H), 2.59 (d, J=0.8 Hz, 3H), 3.34 (dq, J=1.4 and 7.2 Hz,2H), 5.78 (q, J=0.8 Hz, 1H), 6.71 (br s, 1H), 7.34-7.37 (m, 2H), 7.73(ddd, J=1.2, 2.2 and 7.7 Hz, 1H).

Example 86

Potassium carbonate (0.83 g, 6.0 mmol) and tert-butyl isocyanate (0.59g, 6.0 mmol) were added to a solution of5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole (1.15 g, 4.0mmol) in DMF (10 ml), and the mixture was stirred at room temperaturefor 4 hours. After completion of the reaction, the reaction mixture waspoured into 2N hydrochloric acid and extracted with ethyl acetate (20ml×3). An organic layer was washed with water, dried over anhydrousmagnesium sulfate and filtered to remove a desiccant, and the solventwas distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/5), to give a white solid ofN-tert-butyl-5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)-pyrazole-1-carboxamide(0.80 g, yield: 51.8%). mp: 104-106° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.41 (s, 9H), 2.61 (s, 3H), 5.82 (s, 1H), 6.65-6.90 (br s, 1H), 7.43 (d,J=8.7 Hz, 1H), 7.82 (dd, J=2.1 and 8.7 Hz, 1H), 8.23 (d, J=2.1 Hz, 1H).

Examples 87-90

Reactions of 5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole andisocyanates (Example 87: methyl isocyanate, Example 88: ethylisocyanate, Example 89: propyl isocyanate, Example 90: isopropylisocyanate) were carried out in the same manner as in Example 86, togive corresponding N-substituted carboxamides.Products/forms/yields/melting points/NMR spectra are described below.

Example 87

N-methyl-5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamide/whitesolid/yield: 89.0%/mp: 70-72° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.62 (d,J=0.8 Hz, 3H), 2.91 (d, J=5.0 Hz, 3H), 5.88 (q, J=0.8 Hz, 1H), 6.55-6.85(m, 1H), 7.49 (d, J=8.7 Hz, 1H), 7.83 (dd, J=2.0 and 8.7 Hz, 1H), 8.25(d, J=2.0 Hz, 1H).

Example 88

N-ethyl-5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowviscous substance/yield: 25.2%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.21 (t,J=7.3 Hz, 3H), 2.62 (d, J=0.7 Hz, 3H), 3.36 (dq, J=6.0 and 7.3 Hz, 2H),5.87 (q, J=0.7 Hz, 1H), 6.60-6.95 (m, 1H), 7.48 (d, J=8.5 Hz, 1H), 7.85(d, J=2.0 and 8.5 Hz, 1H), 8.25 (d, J=2.0 Hz, 1H).

Example 89

N-propyl-5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowishsolid/yield: 13.6%/mp: 50-51° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.95 (t,J=7.4 Hz, 3H), 1.60 (tq, J=7.1 and 7.4 Hz, 2H), 2.62 (d, J=0.7 Hz, 3H),3.28 (dt, J=6.3 and 7.1 Hz, 2H), 5.87 (q, J=0.7 Hz, 1H), 6.65˜6.95 (m,1H), 7.48 (d, J=8.8 Hz, 1H), 7.85 (dd, J=2.0 and 8.8 Hz, 1H), 8.25 (d,J=2.0 Hz, 1H).

Example 90

N-isopropyl-5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowviscous substance/yield: 70.6%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.24 (d,J=6.6 Hz, 6H), 2.62 (d, J=0.7 Hz, 3H), 3.90-4.10 (m, 1H), 5.86 (q, J=0.7Hz, 1H), 6.50-6.80 (m, 1H), 7.46 (d, J=8.6 Hz, 1H), 7.84 (dd, J=2.0 and8.6 Hz, 1H), 8.25 (d, J=2.0 Hz, 1H).

Example 91

Potassium carbonate (0.61 g, 4.4 mmol) and propyl isocyanate (0.34 g,4.0 mmol) were added to a solution of5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole (1.15 g, 4.0mmol) in ethyl acetate (10 ml), and the mixture was stirred at roomtemperature for 3 hours. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (20 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered co remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/5), to give a yellow viscous substance ofN-propyl-5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole-1-carboxamide(1.08 g, yield: 72.5%). ¹H-NMR (CDCl₃, TMS, ppm): δ 0.97 (t, J=7.4 Hz,3H), 1.62 (tq, J=7.4 and 7.4 Hz, 2H), 2.64 (d, J=0.7 Hz, 3H), 3.25-3.40(m, 2H), 5.88 (q, J=0.7 Hz, 1H), 6.80-7.05 (m, 1H), 7.42 (d, J=9.2 Hz,1H), 8.40 (dd, J=2.7 and 9.2 Hz, 1H), 8.59 (d, J=2.7 Hz, 1H).

Examples 93-95

Reactions of 5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole andisocyanates (Example 93: methyl isocyanate, Example 94: ethylisocyanate, Example 95: isopropyl isocyanate) were carried out in thesame manner as in Example 92, to give corresponding N-substitutedcarboxamides. Products/forms/yields/melting points/NMR spectra aredescribed below.

Example 92

N-methyl-5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole-1-carboxamide/whitesolid/yield: 79.7%/mp: 142-144° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.64 (d,J=0.8 Hz, 3H), 2.95 (d, J=5.0 Hz, 3H), 5.89 (q, J=0.8 Hz, 1H), 6.75-6.95(m, 1H), 7.43 (d, J=9.2 Hz, 1H), 8.40 (dd, J=2.7 and 9.2 Hz, 1H), 8.59(d, J=2.7 Hz, 1H).

Example 93

N-ethyl-5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowishsolid/yield: 86.5%/mp: 95-97° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.24 (t,J=7.3 Hz, 3H), 2.64 (d, J=0.6 Hz, 3H), 3.40 (dq, J=5.9 and 7.3 Hz, 2H),5.88 (q, J=0.6 Hz, 1H), 6.75-7.00 (m, 1H), 7.42 (d, J=9.2 Hz, 1H), 8.38(dd, J=2.8 and 9.2 Hz, 1H), 8.59 (d, J=2.8 Hz, 1H).

Example 94

N-isopropyl-5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole-1-carboxamide/whitesolid/yield: 77.9%/mp: 90-92° C./¹H-NMR (CDCl₃; TMS, ppm): δ 1.26 (d,J=6.6 Hz, 6H), 2.64 (d, J=0.8 Hz, 3H), 4.05 (dq, J=1.4 and 6.6 Hz, 1H),5.86 (q, J=0.8 Hz, 1H), 6.60-6.90 (m, 1H), 7.40 (d, J=9.2 Hz, 1H), 8.40(dd, J=2.7 and 9.2 Hz, 1H), 8.59 (d, J=2.7 Hz, 1H).

Example 95

Potassium carbonate (0.23 g, 1.7 mmol) and ethyl isocyanate (0.11 g, 1.5mmol) were added to a solution of3-(4-cyano-2-trifluoromethylphenyloxy)-5-methylpyrazole (0.40 g, 1.5mmol) in ethyl acetate (10 ml), and the mixture was stirred at roomtemperature overnight. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a yellowish solid ofN-ethyl-3-(4-cyano-2-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.35 g, yield: 69.0%). mp: 103-105° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.23 (t, J=7.3 Hz, 3H), 2.63 (d, J=0.7 Hz, 3H), 3.39 (dq, J=5.9 and 7.2Hz, 2H), 5.85 (q, J=0.7 Hz, 1H), 6.80-7.00 (m, 1H), 7.38 (d, J=8.7 Hz,1H), 7.81 (dd, J=1.8 and 8.7 Hz, 1H), 7.99 (d, J=1.8 Hz, 1H).

Example 96

Triethylamine (0.18 g, 1.8 mmol) and ethyl isocyanate (0.13 g, 1.8 mmol)were added to a solution of5-methyl-3-(3-methyl-4-nitrophenyloxy)pyrazole (0.35 g, 1.5 mmol) inethyl acetate (10 ml), and the mixture was stirred at room temperaturefor 8 hours. After completion of the reaction, the reaction mixture waspoured into 2N hydrochloric acid and extracted with ethyl acetate (10ml×3). An organic layer was washed with water, dried over anhydrousmagnesium sulfate and filtered to remove a desiccant, and the solventwas distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/7), to give a white solid ofN-ethyl-5-methyl-3-(3-methyl-4-nitrophenyloxy)pyrazole-1-carboxamide(0.27 g, yield: 59.2%). mp: 67-69° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.24(t, J=7.3 Hz, 3H), 2.63 (s, 6H), 3.40 (dq, J=5.9 and 7.3 Hz, 2H), 5.79(q, J=0.8 Hz, 1H), 6.85-7.00 (m, 1H), 7.00-7.15 (m, 2H), 8.07 (d, J=8.6Hz, 1H).

Example 97

Reaction of 5-methyl-3-(3-methoxy-4-nitrophenyloxy)pyrazole with ethylisocyanate was carried out in the same manner as in Example 96, to givea yellow viscous substance ofN-ethyl-5-methyl-3-(3-methoxy-4-nitrophenyloxy)pyrazole-1-carboxamide(yield: 62.9%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.24 (t, J=7.2 Hz, 3H), 2.63(d, J=0.6 Hz, 3H), 3.40 (dq, J=5.9 and 7.2 Hz, 2H), 3.95 (s, 3H), 5.81(q, J=0.6 Hz, 1H), 6.75 (dd, J=2.4 and 9.0 Hz, 1H), 6.84 (d, J=2.4 Hz,1H), 6.93 (br s, 1H), 7.96 (d, J=9.0 Hz, 1H).

Example 98

Triethylamine (0.07 g, 0.7 mmol) and ethyl isocyanate (0.12 g, 0.7 mmol)were added to a solution of3-(3-ethoxy-4-nitrophenyloxy)-5-methylpyrazole (0.16 g, 0.6 mmol) inethyl acetate (5 ml) at 0° C., and the mixture was allowed to have roomtemperature gradually and stirred for 5 hours. After completion of thereaction, the reaction mixture was poured into 1N hydrochloric acid (10ml) and extracted with ethyl acetate (10 ml×2). An organic layer waswashed with water (10 ml×2), dried over anhydrous magnesium sulfate andfiltered to remove a desiccant, and the solvent was distilled off fromthe filtrate under reduced pressure. The resultant crude product waspurified with a silica gel column (ethyl acetate/hexane=1/15), to give ayellow solid ofN-ethyl-3-(3-ethoxy-4-nitrophenyloxy)-5-methylpyrazole-1-carboxamide(0.13 g, yield: 61.8%). mp: 110-112° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.24 (t, J=7.3 Hz, 3H), 1.49 (t, J=7.0 Hz, 3H), 2.63 (d, J=0.5 Hz, 3H),3.40 (dq, J=6.0 and 7.3 Hz, 2H), 4.14 (q, J=7.0 Hz, 2H), 5.80 (q, J=0.5Hz, 1H), 6.73 (dd, J=2.4 and 9.0 Hz, 1H), 6.82 (d, J=2.4 Hz, 1H), 6.92(br s, 1H), 7.92 (d, J=9.0 Hz, 1H).

Example 99

Reaction of 3-(5-ethoxy-2-nitrophenyloxy)-5-methylpyrazole with ethylisocyanate was carried out in ethyl acetate in the presence of potassiumcarbonate in the same manner as in Example 99, to give a yellow solid ofN-ethyl-3-(5-ethoxy-2-nitrophenyloxy)-5-methylpyrazole-1-carboxamide(yield: 75.9%). mp: 73-75° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.20 (t,J=7.2 Hz, 3H), 1.44 (t, J=7.0 Hz, 3H), 2.59 (d, J=0.7 Hz, 3H), 3.35 (dq,J=5.9 and 7.2 Hz, 2H), 4.09 (q, J=7.0 Hz, 2H), 5.78 (q, J=0.7 Hz, 1H),6.73 (d, J=2.4 Hz, 1H), 6.77 (dd, J=2.4 and 8.9 Hz, 1H), 6.81 (br s,1H), 8.06 (d, J=8.9 Hz, 1H).

Example 100

Triethylamine (0.13 g, 1.3 mmol) and ethyl isocyanate (0.09 g, 1.3 mmol)were added to a solution of3-(4-amino-3-trifluoromethylphenyloxy)-5-methylpyrazole (0.30 g, 1.2mmol) in ethyl acetate (5 ml) at 0° C., and the mixture was allowed tohave room temperature gradually and stirred for 6 hours. Aftercompletion of the reaction, the reaction mixture was poured into 1Nhydrochloric acid (10 ml) and extracted with ethyl acetate (10 ml×2). Anorganic layer was washed with water (10 ml×2), dried over anhydrousmagnesium sulfate and filtered to remove a desiccant, and the solventwas distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/15), to give a yellowish solid ofN-ethyl-3-(4-amino-3-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.19 g, yield: 50.5%). mp: 102-104° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.22 (t, J=7.3 Hz, 3H), 2.56 (d, J=0.8 Hz, 3H), 3.37 (dq, J=5.9 and 7.3Hz, 2H), 4.11 (br s, 2H), 5.61 (q, J=0.8 Hz, 1H), 6.74 (d, J=8.8 Hz,1H), 6.93 (br s, 1H), 7.14 (dd, J=2.7 and 8.8 Hz, 1H), 7.27 (d, J=2.7Hz, 1H).

Example 101

Triethylamine (0.17 g, 1.7 mmol) and ethyl isocyanate (0.12 g, 1.7 mmol)were added to a solution of3-(4-chloro-3-trifluoromethylphenyloxy)-5-methylpyrazole (0.42 g, 1.5mmol) in ethyl acetate (5 ml) at 0° C., and the mixture was allowed tohave room temperature gradually and stirred for 5 hours. Aftercompletion of the reaction, the reaction mixture was poured into 1Nhydrochloric acid (10 ml) and extracted with ethyl acetate (10 ml×2). Anorganic layer was washed with water (10 ml×2), dried over anhydrousmagnesium sulfate and filtered to remove a desiccant, and the solventwas distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/15), to give a yellow viscous substance ofN-ethyl-3-(4-chloro-3-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.42 g, yield: 80.1%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.22 (t, J=7.2 Hz,3H), 2.59 (d, J=0.8 Hz, 3H), 3.38 (dq, J=5.9 and 7.2 Hz, 2H), 5.73 (q,J=0.8 Hz, 1H), 6.91 (br s, 1H), 7.22 (d, J=8.8 Hz, 1H), 7.49 (dd, J=2.4and 8.8 Hz, 1H), 7.65 (d, J=2.4 Hz, 1H).

Example 102

Potassium carbonate (0.30 g, 2.2 mmol) and propyl isocyanate (0.17 g,2.0 mmol) were added to a solution of5-methyl-3-(4-nitro-3-trifluoromethylphenyloxy)pyrazole (0.57 g, 2.0mmol) in ethyl acetate (10 ml), and the mixture was stirred at roomtemperature overnight. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a yellow viscous substance ofN-propyl-5-methyl-3-(4-nitro-3-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.64 g, yield: 69.0%). ¹H-NMR (CDCl₃, TMS, ppm): δ 0.97 (t, J=7.3 Hz,3H), 1.62 (q, J=7.3 Hz, 2H), 2.64 (s, 3H), 3.32 (dt, J=7.3 and 7.3 Hz,2H), 5.85 (m, 1H), 6.80˜7.05 (m, 1H), 7.45 (dd, J=2.6 and 9.0 Hz, 1H),7.64 (d, J=2.6 Hz, 1H), 8.00 (d, J=9.0 Hz, 1H).

Examples 103-104

Reactions of 5-methyl-3-(4-nitro-3-trifluoromethylphenyloxy)pyrazolewith isocyanates (Example 103: methyl isocyanate, Example 104: ethylisocyanate) were carried out in ethyl acetate in the presence ofpotassium carbonate in the same manner as in Example 102, to givecorresponding N-substituted carboxamides. Products/forms/yields/meltingpoints/NMR spectra are described below.

Example 103

N-methyl-5-methyl-3-(4-nitro-3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowsolid/yield: 42.1%/mp: 139-141° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.65 (d,J=0.4 Hz, 3H), 2.95 (d, J=5.0 Hz, 3H), 5.86 (m, 1H), 6.65-7.00 (m, 1H),7.47 (dd, J=2.6 and 8.9 Hz, 1H), 7.61 (d, J=2.6 Hz, 1H), 8.00 (d, J=8.9Hz, 1H).

Example 104

N-ethyl-5-methyl-3-(4-nitro-3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/yellowishsolid/yield: 34.9%/mp: 95-97° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.24 (t,J=7.3 Hz, 3H), 2.65 (s, 3H), 3.41 (dq, J=5.9 and 7.2 Hz, 2H), 5.85 (m,1H), 6.75-7.00 (m, 1H), 7.45 (dd, J=2.6 and 8.9 Hz, 1H), 7.63 (d, J=2.6Hz, 1H), 8.00 (d, J=8.9 Hz, 1H).

Example 105

Triethylamine (0.40 g, 4.0 mmol) and methyl isocyanate (0.25 g, 4.4mmol) were added to a solution of3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole (1.24 g,4.0 mmol) in ethyl acetate (20 ml), and the mixture was stirred at roomtemperature for 6 hours. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (20 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-methyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.87 g, yield: 59.0%). mp: 113-114° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ2.60 (d, J=0.7 Hz, 3H), 2.88 (d, J=4.9 Hz, 3H), 5.77 (d, J=0.7 Hz, 1H),6.50-6.75 (m, 1H), 7.66 (s, 2H).

Example 106

Potassium carbonate (0.30 g, 2.2 mmol) and ethyl isocyanate (0.14 g, 2.0mmol) were added to a solution of3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole (0.62 g,2.0 mmol) in ethyl acetate (10 ml), and the mixture was stirred at roomtemperature for 4 hours. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-ethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.48 g, yield: 62.8%). mp: 80-82° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.19(t, J=7.3 Hz, 3H), 2.59 (s, 3H), 3.34 (dq, J=6.1 and 7.3 Hz, 2H), 5.72(s, 1H), 6.60-6.85 (m, 1H), 7.67 (s, 2H).

Examples 107-117

Reactions of3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole withisocyanates (Example 107: propyl isocyanate, Example 108: isopropylisocyanate, Example 109: tert-butyl isocyanate, Example 110: hexylisocyanate, Example 111: octyl isocyanate, Example 112: allylisocyanate, Example 113: 2-chloroethyl isocyanate, Example 114:2-bromoethyl isocyanate, Example 115: benzyl isocyanate, Example 116:ethyl isocyanatoacetate, Example 117: ethyl 3-isocyanatopropionate) werecarried out in ethyl acetate in the presence of a base in the samemanner as in Example 105 or 106, to give corresponding N-substitutedcarboxamides. Products/forms/yields/melting points/NMR spectra aredescribed below.

Example 107

N-propyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substance/yield: 68.4%/¹H-NMR (CDCl₃, TMS, ppm): δ 0.92 (t,J=7.5 Hz, 3H), 1.59 (tq, J=7.5 and 7.8 Hz, 2H), 2.58 (d, J=0.8 Hz, 3H),3.25 (m, 2H), 5.71 (q, J=0.8 Hz, 1H), 6.70-6.90 (m, 1H), 7.66 (s, 2H).

Example 108

N-isopropyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 68.4%/mp: 103-105° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.22 (d,J=6.5 Hz, 6H), 2.57 (d, J=0.8 Hz, 3H), 3.90-4.10 (m, 1H), 5.62 (q, J=0.8Hz, 1H), 6.50-6.75 (m, 1H), 7.67 (s, 2H).

Example 109

N-tert-butyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 54.8%/mp: 116-117° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.40 (s,9H), 2.56 (s, 3H), 5.57 (s, 1H), 6.70-6.85 (m, 1H), 7.67 (s, 2H).

Example 110

N-hexyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substance/yield: 69.5%/¹H-NMR (CDCl₃, TMS, ppm): δ 0.88 (t,J=6.8 Hz, 3H), 1.15-1.40 (m, 6H), 1.45-1.65 (m, 2H), 2.58 (s, 3H),3.15-3.40 (m, 2H), 5.71 (s, 1H), 6.65-6.85 (m, 1H), 7.66 (s, 2H).

Example 111

N-octyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 64.3%/mp: 43-45° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.88 (t,J=6.8 Hz, 3H), 1.10-1.45 (m, 10H), 1.45-1.65 (m, 2H), 2.58 (s, 3H),3.15-3.35 (m, 2H), 5.70 (s, 1H), 6.65-6.85 (m, 1H), 7.66 (s, 2H).

Example 112

N-allyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substance/yield: 83.1%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.59 (d,J=0.8 Hz, 3H), 3.80-4.00 (m, 2H), 5.05-5.30 (m, 2H), 5.75 (q, J=0.8 Hz,1H), 5.75-5.95 (m, 1H), 6.70-7.00 (m, 1H), 7.66 (s, 2H).

Example 113

N-(2-chloroethyl)-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 62.4%/mp: 116-118° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.58 (s,3H), 3.50-3.75 (m, 4H), 5.76 (s, 1H), 6.95-7.20 (m, 1H), 7.67 (s, 2H).

Example 114

N-(2-bromoethyl)-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 58.6%/mp: 106-107° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.58 (s,3H), 3.48 (t, J=6.1 Hz, 2H), 3.69 (dt, J=6.1 and 6.1 Hz, 2H), 5.77 (s,1H), 6.95-7.20 (m, 1H), 7.67 (s, 2H).

Example 115

N-benzyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 76.5%/mp: 50-53° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.61 (d,J=0.7 Hz, 3H), 4.40 (d, J=6.2 Hz, 2H), 5.74 (q, J=0.7 Hz, 1H), 7.13 (brt, J=6.2 Hz, 1H), 7.25-7.40 (m, 5H), 7.65 (s, 2H).

Example 116

ethyl[{3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazol-1-yl}carbonylamino]acetate/whitesolid/yield: 76.5%/mp: 50-53° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.27 (t,J=7.1 Hz, 3H), 2.58 (d, J=0.7 Hz, 3H), 4.04 (d, J=5.9 Hz, 2H), 4.21 (q,J=7.2 Hz, 2H), 5.80 (q, J=0.7 Hz, 1H), 7.10 (br t, J=5.9 Hz, 1H), 7.66(s, 2H).

Example 117

ethyl3-[{3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazol-1-yl}carbonylamino]propionate/whitesolid/yield: 77.2%/mp: 73-74° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.20 (t,J=7.5 Hz, 3H), 2.50-2.65 (m, 4H), 3.56 (q, J=7.5 Hz, 2H), 4.00-4.20 (m,2H), 5.76 (q, J=0.8 Hz, 1H), 7.00-7.20 (m, 2H), 7.66 (s, 2H).

Example 118

Triethylamine (0.13 g, 1.3 mmol) and methyl isocyanate (0.07 g, 1.2mmol) were added to a solution of3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole (0.32g, 1.1 mmol) in ethyl acetate (10 ml), and the mixture was stirred atroom temperature for 4 hours. After completion of the reaction, thereaction mixture was poured into 2N hydrochloric acid and extracted withethyl acetate (10 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-methyl-3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.22 g, yield: 56.9%). mp: 87-88° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.59(s, 3H), 2.88 (d, J=5.0 Hz, 3H), 5.80 (s, 1H), 6.55-6.75 (m, 1H), 7.40(dd, J_(HF)=2.0 and 9.3 Hz, 1H), 7.56 (s, 1H).

Examples 119-123

Reactions of3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole withisocyanates (Example 119: ethyl isocyanate, Example 120: isopropylisocyanate, Example 121: propyl isocyanate, Example 122: allylisocyanate, Example 123: 2-bromoethyl isocyanate) were carried out inthe same manner as in Example 118, to give corresponding N-substitutedcarboxamides. Products/forms/yields/melting points/NMR spectra aredescribed below.

Example 119

N-ethyl-3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 42.8%/mp: 58-60° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.19 (t,J=7.3 Hz, 3H), 2.59 (d, J=0.7 Hz, 3H), 3.34 (dq, J=6.0 and 7.2 Hz, 2H),5.76 (q, J=0.7 Hz, 1H), 6.60-6.85 (m, 1H), 7.40 (dd, J_(HF)=1.8 and 9.2Hz, 1H), 7.57 (s, 1H).

Example 120

N-isopropyl-3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substance/yield: 31.1%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.22 (d,J=6.6 Hz, 6H), 2.58 (d, J=0.8 Hz, 3H), 4.01 (dsep, J=6.6 and 6.6 Hz,1H), 5.69 (q, J=0.8 Hz, 1H), 6.60 (br d, J=6.6 Hz, 1H), 7.41 (dd,J_(HF)=1.8 and 9.2 Hz, 1H), 7.58 (s, 1H).

Example 121

N-propyl-3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substrate/yield: 49.5%/¹H-NMR (CDCl₃, TMS, ppm): δ 0.92 (t,J=7.4 Hz, 3H), 1.58 (tq, J=7.4 and 13.3 Hz, 3H), 2.58 (d, J=0.8 Hz, 3H),3.25 (dt, J=6.4 and 13.3 Hz, 1H), 5.76 (q, J=0.8 Hz, 1H), 6.65-6.90 (m,1H), 7.40 (dd, J=2.0 and 9.4 Hz, 1H), 7.57 (s, 1H).

Example 122

N-allyl-3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substrate/yield: 50.7%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.59 (d,J=0.8 Hz, 3H), 3.92 (ddt, J=1.6, 5.8 and 5.8 Hz, 2H), 5.10-5.25 (m, 2H),5.79 (q, J=0.8 Hz, 1H), 5.75-5.95 (m, 1H), 6.70-7.00 (m, 1H), 9.40 (dd,J_(HF)=2.1 and 9.5 Hz, 1H), 7.57 (s, 1H).

Example 123

N-(2-bromoethyl)-3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 63.7%/mp: 85-86° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.58 (d,J=0.8 Hz, 3H), 3.48 (t, J=6.3 Hz, 2H), 3.70 (dt, J=6.3 and 6.3 Hz, 2H),5.81 (d, J=0.8 Hz, 1H), 7.09 (br t, J=6.3 Hz, 1H), 7.40 (dd, J_(HF)=1.8and 9.3 Hz, 1H), 7.57 (s, 1H).

Example 124

Triethylamine (0.20 g, 2.0 mmol) and ethyl isocyanate (0.14 g, 2.0 mmol)were added to a solution of3-(2,6-difluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole (0.42 g,1.5 mmol) in ethyl acetate (10 ml), and the mixture was stirred at roomtemperature for 12 hours. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column(chloroform), to give a white solid ofN-ethyl-3-(2,6-difluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.11 g, yield: 21.0%). mp: 102-104° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.21 (t, J=7.3 Hz, 3H), 2.19 (s, 3H), 3.32 (dq, J=6.0 and 7.3 Hz, 2H),5.00-5.25 (m, 1H), 6.25 (s, 1H), 7.36 (d, J_(HF)=7.0 Hz, 2H).

Example 125

Potassium carbonate (0.15 g, 1.1 mmol) and ethyl isocyanate (0.07 g, 1.0mmol) were added to a solution of3-(2,4-dinitro-6-trifluoromethylphenyloxy)-5-methylpyrazole (0.33 g, 1.0mmol) in ethyl acetate (10 ml), and the mixture was stirred at roomtemperature for 12 hours. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a yellowish solid ofN-ethyl-3-(2,4-dinitro-6-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.20 g, yield: 49.6%). mp: 169-171° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.18 (t, J=7.2 Hz, 3H), 2.59 (d, J=0.4 Hz, 3H), 3.31 (dq, J=6.0 and 7.2Hz, 2H), 5.95 (q, J=0.4 Hz, 1H), 6.25-6.50 (m, 1H), 8.85 (d, J=2.7 Hz,1H), 9.02 (d, J=2.7 Hz, 1H).

Example 126

Potassium carbonate (0.30 g, 2.2 mmol) and ethyl isocyanate (0.14 g, 2.0mmol) were added to a solution of3-(2-chloro-6-nitro-4-trifluoromethylphenyloxy)-5-methylpyrazole (0.64g, 2.0 mmol) in ethyl acetate (10 ml), and the mixture was stirred atroom temperature overnight. After completion of the reaction, thereaction mixture was poured into 2N hydrochloric acid and extracted withethyl acetate (10 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a yellowish solid ofN-ethyl-3-(2-chloro-6-nitro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.13 g, yield: 16.6%). mp: 98-99° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.18(t, J=7.2 Hz, 3H), 2.60 (d, J=0.5 Hz, 3H), 3.32 (dq, J=6.0 and 7.2 Hz,2H), 5.87 (q, J=0.5 Hz, 1H), 6.40-6.65 (m, 1H), 8.01 (d, J=2.0 Hz, 1H),8.17 (m, 1H).

Examples 127-128

Reactions of3-(2-chloro-6-nitro-4-trifluoromethylphenyloxy)-5-methylpyrazole andisocyanates (Example 127: methyl isocyanate, Example 128: propylisocyanate) were carried out in ethyl acetate in the presence ofpotassium carbonate in the same manner as in Example 126, to givecorresponding N-substituted carboxamides. Products/forms/yields/meltingpoints/NMR spectra are described below.

Example 127

N-methyl-3-(2-chloro-6-nitro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 60.9%/mp: 140-142° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.60 (d,J=0.6 Hz, 3H), 2.87 (d, J=5.0 Hz, 3H), 5.89 (q, J=0.6 Hz, 1H), 6.40-6.55(m, 1H), 8.01 (d, J=2.0 Hz, 1H), 8.19 (m, 1H).

Example 128

N-propyl-3-(2-chloro-6-nitro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 34.4%/mp: 111-113° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.92 (t,J=7.4 Hz, 3H), 1.57 (m, 2H), 2.19 (s, 3H), 3.23 (dt, J=7.4 and 7.4 Hz,2H), 5.88 (s, 1H), 6.45-6.70 (m, 1H), 8.01 (d, J=2.1 Hz, 1H), 8.17 (m,1H).

Example 129

Potassium carbonate (0.30 g, 2.2 mmol) and ethyl isocyanate (0.14 g, 2.0mmol) were added to a solution of3-(3,5-dichloropyridin-2-yloxy)-5-methylpyrazole (0.49 g, 2.0 mmol) inethyl acetate (10 ml), and the mixture was stirred at room temperatureovernight. After completion of the reaction, the reaction mixture waspoured into 2N hydrochloric acid and extracted with ethyl acetate (10ml×3). An organic layer was washed with water, dried over anhydrousmagnesium sulfate and filtered to remove a desiccant, and the solventwas distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-ethyl-3-(3,5-dichloropyridin-2-yloxy)-5-methylpyrazole-1-carboxamide(0.44 g, yield: 69.8%). mp: 74-76° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.23(t, J=7.2 Hz, 3H), 2.64 (s, 3H), 3.39 (dq, J=5.8 and 7.2 Hz, 2H), 6.00(s, 1H), 6.90-7.15 (m, 1H), 7.80 (d, J=2.3 Hz, 1H), 8.05 (d, 2.3 Hz,1H).

Example 130

Triethylamine (0.22 g, 2.2 mmol) was added to a solution of5-methyl-3-(6-methoxy-3-nitropyridin-2-yloxy)pyrazole (0.5 g, 2.0 mmol)in ethyl acetate (10 ml), and the mixture was cooled to 0° C. Ethylisocyanate (0.16 g, 2.2 mmol) was added, and the mixture was stirred atan ambient temperature for 30 minutes. The mixture was allowed to haveroom temperature. After completion of the reaction, the reaction mixturewas poured into 1N hydrochloric acid (10 ml) and extracted with ethylacetate (10 ml×2). An organic layer was washed with water (10 ml×2),dried over anhydrous magnesium sulfate and filtered to remove adesiccant, and the solvent was distilled off from the filtrate underreduced pressure. The resultant crude product was purified with a silicagel column (ethyl acetate/hexane=1/6), to give a yellow viscoussubstance ofN-ethyl-5-methyl-3-(6-methoxy-3-nitropyridin-2-yloxy)pyrazole-1-carboxamide(0.38 g, yield: 59.8%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.24 (t, J=7.3 Hz,3H), 2.65 (d, J=0.8 Hz, 3H), 3.40 (dq, J=1.4 and 7.3 Hz, 2H), 3.84 (s,3H), 6.02 (q, J=0.8 Hz, 1H), 6.57 (dd, J=3.5 and 8.8 Hz, 1H), 7.05 (brs, 1H), 8.41 (dd, J=3.5 and 8.8 Hz, 1H).

Example 131

Reaction of 5-methyl-3-(4-methyl-5-nitropyridin-2-yloxy)pyrazole withethyl isocyanate was carried out in the presence of triethylamine in thesame manner as in Example 130, to give a yellow viscous substance ofN-ethyl-5-methyl-3-(4-methyl-5-nitropyridin-2-yloxy)pyrazole-1-carboxamide(yield: 19.3%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.23 (t, J=7.3 Hz, 3H), 2.65(d, J=0.7 Hz, 3H), 2.70 (s, 3H), 3.40 (dq, J=5.9 and 7.3 Hz, 2H), 6.03(q, J=0.7 Hz, 1H), 6.95 (s, 1H), 6.99 (br s, 1H), 8.92 (s, 1H).

Example 132

Potassium carbonate (0.75 g, 5.4 mmol) and isopropyl isocyanate (0.46 g,5.4 mmol) were added to a solution of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole (1.00 g,3.6 mmol) in ethyl acetate (10 ml), and the mixture was stirred at roomtemperature for 3 hours. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a colorless viscous substance ofN-isopropyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide(0.91 g, yield: 69.7%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.25 (d, J=6.5 Hz,6H), 2.65 (d, J=0.8 Hz, 3H), 3.95-4.20 (m, 1H), 6.04 (q, J=0.8 Hz, 1H),6.80˜7.00 (m, 1H), 8.02 (d, J=2.3 Hz, 1H), 8.35 (m, 1H).

Examples 133-150

Reactions of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole andisocyanates (Example 133: methyl isocyanate, Example 134: ethylisocyanate, Example 135: propyl isocyanate, Example 136: tert-butylisocyanate, Example 137: pentyl isocyanate, Example 138: hexylisocyanate, Example 139: heptyl isocyanate, Example 140: octylisocyanate, Example 141: dodecyl isocyanate, Example 142: cyclohexylisocyanate, Example 143: allyl isocyanate, Example 144: 2-chloroethylisocyanate, Example 145: phenyl isocyanate, Example 146: 3-chlorophenylisocyanate, Example 147: 3,4-dichlorophenyl isocyanate, Example 148:3-trifluoromethylphenyl isocyanate, Example 149: 4-trifluoromethylphenylisocyanate, Example 150: 3-nitrophenyl isocyanate) were carried out inthe same manner as in Example 132, to give corresponding N-substitutedcarboxamides. Products/forms/yields/melting points/NMR spectra aredescribed below.

Example 133

N-methyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 81.7%/mp: 85-86° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.66 (d,J=0.8 Hz, 3H), 2.95 (d, J=5.0 Hz, 3H), 6.05 (q, J=0.8 Hz, 1H), 6.85-7.15(m, 1H), 8.01 (d, J=2.0 Hz, 1H), 8.35 (m, 1H).

Example 134

N-ethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 55.8%/mp: 85-86° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.23 (t,J=7.3 Hz, 3H), 2.66 (s, 3H), 3.40 (dq, J=6.0 and 7.3 Hz, 2H), 6.04 (s,1H), 6.90-7.15 (m, 1H), 8.02 (d, J=2.0 Hz, 1H), 8.35 (m, 1H).

Example 135

N-propyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substance/yield: 86.3%/¹H-NMR (CDCl₃, TMS, ppm): δ 0.97 (t,J=7.3 Hz, 3H), 1.60 (tq, J=7.3 and 7.3 Hz, 2H), 2.66 (d, J=0.8 Hz, 3H),3.30 (dt, J=6.5 and 7.3 Hz, 2H), 6.05 (q, J=0.8 Hz, 1H), 6.95-7.20 (m,1H), 8.02 (d, J=2.0 Hz, 1H), 8.35 (m, 1H).

Example 136

N-tert-butyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substance/yield: 74.5%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.44 (s, 9H),2.64 (d, J=0.7 Hz, 3H), 6.02 (q, J=0.7 Hz, 1H), 6.90-7.15 (br s, 1H),8.01 (d, J=2.1 Hz, 1H), 8.34 (m, 1H).

Example 137

N-pentyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/yellowishsolid/yield: 73.2%/mp: 142-144° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.90 (t,J=7.0 Hz, 3H), 1.20-1.45 (m, 4H), 1.50-1.70 (m, 2H), 2.66 (d, J=0.8 Hz,3H), 3.25-3.40 (m, 2H), 6.04 (q, J=0.8 Hz, 1H), 6.95-7.15 (m, 1H), 8.02(d, J=2.3 Hz, 1H), 8.25-8.40 (m, 1H).

Example 138

N-hexyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substance/yield: 65.2%/¹H-NMR (CDCl₃, TMS, ppm): δ 0.89 (t,J=6.8 Hz, 3H), 1.15-1.45 (m, 6H), 1.45-1.70 (m, 2H), 2.65 (d, J=0.8 Hz,3H), 3.25-3.45 (m, 2H), 6.04 (q, J=0.8H, 1H), 6.95-7.15 (m, 1H), 8.02(d, J=2.0 Hz, 1H), 8.35 (m, 1H).

Example 139

N-heptyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substance/yield: 84.9%/¹H-NMR (CDCl₃, TMS, ppm): δ 0.75-1.00 (m,3H), 1.10-1.50 (m, 8H), 1.50-1.70 (m, 2H), 2.65 (s, 3H), 3.20-3.45 (m,2H), 6.04 (s, 1H), 6.95-7.15 (m, 1H), 8.02 (d, J=2.0 Hz, 1H), 8.36 (m,1H).

Example 140

N-octyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substance/yield: 81.5%/¹H-NMR (CDCl₃, TMS, ppm): δ 0.88 (t,J=7.0 Hz, 3H), 1.15-1.45 (m, 10H), 1.45-1.75 (m, 2H), 2.66 (d, J=0.5 Hz,3H), 3.20-3.45 (m, 2H), 6.04 (s, 1H), 6.95-7.15 (m, 1H), 8.02 (d, J=2.0Hz, 1H), 8.35 (m, 1H).

Example 141

N-dodecyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 80.7%/mp: 56-57° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.88 (t,J=6.9 Hz, 3H), 1.20-1.40 (m, 18H), 1.50-1.65 (m, 2H), 2.65 (d, J=0.8 Hz,3H), 3.25-3.40 (m, 2H), 6.04 (q, J=0.8 Hz, 1H), 6.95-7.15 (m, 1H), 8.03(d, J=2.1 Hz, 1H), 8.38 (m, 1H).

Example 142

N-cyclohexyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 65.5%/mp: 69-71° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.05-1.50(m, 6H), 1.55-1.85 (m, 2H), 1.90-2.10 (m, 2H), 2.65 (d, J=0.8 Hz, 3H),3.60-3.85 (m, 1H), 6.03 (q, J=0.8 Hz, 1H), 6.80-7.05 (m, 1H), 8.01 (d,J=2.0 Hz, 1H), 8.35 (m, 1H).

Example 143

N-allyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substance/yield: 62.2%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.66 (d,J=0.8 Hz, 3H), 3.85-4.05 (m, 2H), 5.05-5.35 (m, 2H), 5.75-6.00 (m, 1H),6.06 (q, J=0.8 Hz, 1H), 7.05-7.25 (m, 1H), 8.02 (d, J=2.3 Hz, 1H), 8.35(m, 1H).

Example 144

N-(2-chloroethyl)-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 65.2%/mp: 98-100° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.65 (d,J=0.5 Hz, 3H), 3.65-3.75 (m, 4H), 6.08 (q, J=0.5 Hz, 1H), 7.30-7.50 (m,1H), 8.03 (d, J=1.8 Hz, 1H), 8.36 (m, 1H).

Example 145

N-phenyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 4.9%/mp: 116-118° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.72 (d,J=0.8 Hz, 3H), 6.12 (q, J=0.8 Hz, 1H), 7.10-7.20 (m, 1H), 7.30-7.45 (m,2H), 7.50-7.60 (m, 2H), 8.05 (d, J=2.2 Hz, 1H), 8.40 (m, 1H), 8.85-9.10(m, 1H).

Example 146

N-(3-chlorophenyl)-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 36.0%/mp: 129-130° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.72 (d,J=0.7 Hz, 3H), 6.15 (q, J=0.7 Hz, 1H), 7.05-7.15 (m, 1H), 7.20-7.30 (m,1H), 7.30-7.40 (m, 1H), 7.73 (t, J=2.0 Hz, 1H), 8.05 (d, J=1.8 Hz, 1H),8.30-8.40 (m, 1H), 8.90-9.10 (br s, 1H).

Example 147

N-(3,4-dichlorophenyl)-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 38.1%/mp: 150-152° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.71 (s,3H), 6.15 (s, 1H), 7.30-7.45 (m, 2H), 7.83 (d, J=2.3 Hz, 1H), 8.00˜8.10(m, 1H), 8.25-8.45 (m, 1H), 9.01 (s, 1H).

Example 148

N-(3-trifluoromethylphenyl)-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 18.0%/mp: 123-124° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.73 (d,J=0.8 Hz, 3H), 6.16 (q, J=0.8 Hz, 1H), 7.45 (dt, J=8.0 and 8.0 Hz, 2H),7.72 (d, J=8.0 Hz, 1H), 7.93 (s, 1H), 8.05 (d, J=8.0 Hz, 1H), 8.37 (m,1H), 9.00-9.25 (br s, 1H).

Example 149

N-(4-trifluoromethylphenyl)-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 24.4%/mp: 164-167° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.73 (d,J=0.7 Hz, 3H), 6.16 (q, J=0.7 Hz, 1H), 7.62 (d, J=8.8 Hz, 2H), 7.70 (d,J=8.8 Hz, 2H), 8.05 (d, J=2.1 Hz, 1H), 8.30-8.45 (m, 1H), 9.10-9.25 (brs, 1H).

Example 150

N-(3-nitrophenyl)-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 13.6%/mp: 172-174° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.73 (s,3H), 6.18 (s, 1H), 7.54 (t, J=8.2 Hz, 1H), 7.88 (dd, J=0.9 and 2.2 Hz,1H), 8.03 (dd, J=0.9 and 2.2 Hz, 1H), 8.06 (d, J=2.1 Hz, 1H), 8.37 (m,1H), 8.54 (t, J=2.1 Hz, 1H), 9.15-9.30 (m, 1H).

Example 151

Potassium carbonate (0.50 g, 3.6 mmol) and methyl isocyanate (0.17 g,3.0 mmol) were added to a solution of4,5-dimethyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole (1.08 g, 3.6mmol) in ethyl acetate (20 ml), and the mixture was stirred at roomtemperature overnight. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with diethylether (20 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/3), to give a yellow solid ofN-methyl-4,5-dimethyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.93 g, yield: 86.5%). mp: 117-119° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.95 (s, 3H), 2.55 (s, 3H), 2.90 (d, J=5.0 Hz, 3H), 6.50-6.80 (m, 1H),7.49 (d, J=8.7 Hz, 1H), 7.84 (dd, J=2.0 and 8.7 Hz, 1H), 8.25 (d, J=2.0Hz, 1H).

Example 152

Potassium carbonate (0.50 g, 3.6 mmol) and methyl isocyanate (0.17 g,3.0 mmol) were added to a solution of4,5-dimethyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole (1.08 g, 3.6mmol) in ethyl acetate (20 ml), and the mixture was stirred at roomtemperature overnight. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with diethylether (20 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/3), to give a white solid ofN-methyl-4,5-dimethyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.88 g, yield: 81.9%). mp: 113-115° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.88 (s, 3H), 2.57 (s, 3H), 2.94 (d, J=5.0 Hz, 3H), 6.70-6.95 (m, 1H),7.44 (d, J=9.2 Hz, 1H), 8.39 (dd, J=2.7 and 9.2 Hz, 1H), 8.60 (d, J=2.7Hz, 1H).

Example 153

Potassium carbonate (0.62 g, 4.5 mmol) and isopropyl isocyanate (0.26 g,3.0 mmol) were added to a solution of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-4,5-dimethylpyrazole (0.88g, 3.0 mmol) in DMF (10 ml), and the mixture was stirred at roomtemperature for 6 hours. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/5), to give a white solid ofN-isopropyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-4,5-dimethylpyrazole-1-carboxamide(0.55 g, yield: 48.7%) mp: 78-80° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.24(d, J=6.6 Hz, 6H), 1.78 (s, 3H), 2.58 (s, 3H), 3.95-4.15 (m, 1H),6.70-6.95 (m, 1H), 8.02 (d, J=2.1 Hz, 1H), 8.32 (m, 1H).

Examples 154-155

Reactions of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-4,5-dimethylpyrazole andisocyanates (Example 154: methyl isocyanate, Example 155: ethylisocyanate) were carried out in the same manner as in Example 153, togive corresponding N-substituted carboxamides.Products/forms/yields/melting points/NMR spectra are described below.

Example 154

N-methyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-4,5-dimethylpyrazole-1-carboxamide/whitesolid/yield: 92.3%/mp: 117-118° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.80 (s,3H), 2.58 (s, 3H), 2.93 (d, J=4.9 Hz, 3H), 6.80-7.10 (m, 1H), 8.02 (d,J=2.0 Hz, 1H), 8.32 (m, 1H).

Example 155

N-ethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-4,5-dimethylpyrazole-1-carboxamide/whitesolid/yield: 38.6%/mp: 124-125° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.21 (t,J=7.3 Hz, 3H), 1.79 (s, 3H), 2.58 (s, 3H), 3.38 (dq, J=6.0 and 7.2 Hz,2H), 6.85-7.10 (m, 1H), 8.02 (d, J=2.1 Hz, 1H), 8.32 (m, 1H).

Example 156

Potassium carbonate (0.50 g, 3.6 mmol) and methyl isocyanate (0.17 g,3.0 mmol) were added to a solution of4-ethyl-5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole (1.13 g,3.6 mmol) in ethyl acetate (20 ml), and the mixture was stirred at roomtemperature overnight. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with diethylether (20 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/3), to give a yellow solid ofN-methyl-4-ethyl-5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.62 g, yield: 55.5%). mp: 81-82° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.14(t, J=7.6 Hz, 3H), 2.41 (q, J=7.6 Hz, 2H), 2.56 (s, 3H), 2.90 (d, J=5.0Hz, 3H), 6.50-6.75 (m, 1H), 7.51 (d, J=8.7 Hz, 1H), 7.84 (dd, J=2.1 and8.7 Hz, 1H), 8.26 (d, J=2.1 Hz, 1H).

Example 157

Potassium carbonate (0.50 g, 3.6 mmol) and methyl isocyanate (0.17 g,3.0 mmol) were added to a solution of4-ethyl-5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole (1.13 g,3.6 mmol) in ethyl acetate (15 ml), and the mixture was stirred at roomtemperature overnight. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with diethylether (20 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/3), to give a yellow solid ofN-methyl-4-ethyl-5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.71 g, yield: 63.6%). mp: 96-97° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.08(t, J=7.6 Hz, 3H), 2.35 (q, J=7.6 Hz, 2H), 2.59 (s, 3H), 2.94 (d, J=5.0Hz, 3H), 6.70-6.90 (m, 1H), 7.48 (d, J=9.2 Hz, 1H), 8.40 (dd, J=2.7 and9.2 Hz, 1H), 8.60 (d, J=2.7 Hz, 1H).

Example 158

Potassium carbonate (0.83 g, 6.0 mmol) and methyl isocyanate (0.29 g,5.0 mmol) were added to a solution of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-4-ethyl-5-methylpyrazole(1.83 g, 6.0 mmol) in ethyl acetate (25 ml), and the mixture was stirredat room temperature overnight. After completion of the reaction, thereaction mixture was poured into 2N hydrochloric acid and extracted withdiethyl ether (30 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column (ethylacetate/hexane=1/5), to give a white solid ofN-methyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-4-ethyl-5-methylpyrazole-1-carboxamide(1.14 g, yield: 62.9%). mp: 84-86° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.04(t, J=7.6 Hz, 3H), 2.26 (q, J=7.6 Hz, 2H), 2.59 (s, 3H), 2.93 (d, J=5.0Hz, 3H), 6.80-7.05 (m, 1H), 8.02 (d, J=2.0 Hz, 1H), 8.32 (m, 1H).

Example 159

Reaction of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-4-ethyl-5-methylpyrazolewith ethyl isocyanate was carried out in the same manner as in Example158, to give a white solid ofN-ethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-4-ethyl-5-methylpyrazole-1-carboxamide(0.36 g, yield: 31.9%). mp: 101-102° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.03 (t, J=7.6 Hz, 3H), 1.21 (t, J=7.3 Hz, 3H), 2.25 (q, J=7.6 Hz, 2H),2.59 (s, 3H), 3.38 (dq, J=5.9 and 7.3 Hz, 2H), 6.85-7.05 (m, 1H), 8.02(d, J=2.0 Hz, 1H), 8.32 (m, 1H).

Example 160

Triethylamine (0.10 g, 1.0 mmol) and 2-chloroethyl isocyanate (0.12 g,1.1 mmol) were added to a solution of4-chloro-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole(0.35 g, 1.0 mmol) in ethyl acetate (10 ml), and the mixture was stirredat room temperature for 8 hours. After completion of the reaction, thereaction mixture was poured into 2N hydrochloric acid and extracted withethyl acetate (10 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-(2-chloroethyl)-4-chloro-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.44 g, yield: 97.6%). mp: 141-143° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ2.62 (s, 3H), 3.55-3.65 (m, 4H), 6.80-7.05 (m, 1H), 7.67 (s, 2H).

Example 161

Potassium carbonate (0.72 g, 5.2 mmol) and methyl isocyanate (0.29 g,5.0 mmol) were added to a solution of5-ethyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole (1.58 g, 5.2mmol) in ethyl acetate (20 ml), and the mixture was stirred at roomtemperature overnight. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with diethylether (20 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a yellow solid ofN-methyl-5-ethyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.68 g, yield: 38.0%). mp: 89-91° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.29(t, J=7.4 Hz, 3H), 2.91 (d, J=5.0 Hz, 3H), 3.09 (q, J=7.4 Hz, 2H), 5.92(s, 1H), 6.55-6.85 (m, 1H), 7.50 (d, J=8.7 Hz, 1H), 7.85 (dd, J=2.1 and8.7 Hz, 1H), 8.26 (d, J=2.1 Hz, 1H).

Example 162

Potassium carbonate (0.83 g, 6.0 mmol) and methyl isocyanate (0.29 g,5.0 mmol) were added to a solution of5-ethyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole (1.81 g, 6.0mmol) in ethyl acetate (15 ml), and the mixture was stirred at roomtemperature overnight. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with diethylether (20 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/7), to give a yellow solid ofN-methyl-5-ethyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole-1-carboxamide(1.42 g, yield: 79.3%). mp: 97-100° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.30(t, J=7.5 Hz, 3H), 2.95 (d, J=5.0 Hz, 3H), 3.12 (q, J=7.5H, 2H), 5.93(s, 1H), 6.75-7.00 (m, 1H), 7.45 (d, J=9.2 Hz, 1H), 8.41 (dd, J=2.7 and9.2 Hz, 1H), 8.60 (d, J=2.7 Hz, 1H).

Example 163

Potassium carbonate (0.46 g, 3.3 mmol) and ethyl isocyanate (0.21 g, 3.0mmol) were added to a solution of3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-ethylpyrazole (0.98 g, 3.0mmol) in ethyl acetate (10 ml), and the mixture was stirred at roomtemperature for 6 hours. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-ethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-ethylpyrazole-1-carboxamide(0.79 g, yield: 66.5%). mp: 86-89° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.19(t, J=7.3 Hz, 3H), 1.27 (t, J=7.5 Hz, 3H), 3.06 (q, J=7.5 Hz, 2H), 3.34(dq, J=6.1 and 7.3 Hz, 2H), 5.75 (s, 1H), 6.60-6.85 (m, 1H), 7.68 (s,2H).

Example 164

Potassium carbonate (1.16 g, 8.4 mmol) and methyl isocyanate (0.40 g,7.0 mmol) were added to a solution of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-ethylpyrazole (2.45 g,8.4 mmol) in ethyl acetate (30 ml), and the mixture was stirred at roomtemperature overnight. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with diethylether (30 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/5), to give a white solid ofN-methyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-ethylpyrazole-1-carboxamide(1.97 g, yield: 80.7%). mp: 85-87° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.31(t, J=7.5 Hz, 3H), 2.95 (d, J=5.0 Hz, 3H), 3.13 (dq, J=6.0 and 7.5 Hz,2H), 6.08 (s, 1H), 6.85-7.15 (m, 1H), 8.02 (d, J=2.1 Hz, 1H), 8.36 (m,1H).

Example 165

Reaction of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-ethylpyrazole with ethylisocyanate was carried out in the same manner as in Example 164, to givea white solid ofN-ethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-ethylpyrazole-1-carboxamide(0.25 g, yield: 23.0%). mp: 85-86° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.23(t, J=7.3 Hz, 3H), 1.30 (t, J=7.5 Hz, 3H), 3.13 (q, J=7.5 Hz, 2H), 3.40(dq, J=5.9 and 7.3 Hz, 2H), 6.08 (s, 1H), 6.90-7.15 (m, 1H), 8.02 (d,J=2.1 Hz, 1H), 8.37 (m, 1H).

Example 166

Potassium carbonate (0.23 g, 1.7 mmol) and ethyl isocyanate (0.11 g, 1.5mmol) were added to a solution of5-cyclopropyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)pyrazole (0.51g, 1.5 mmol) in ethyl acetate (10 ml), and the mixture was stirred atroom temperature overnight. After completion of the reaction, thereaction mixture was poured into 2N hydrochloric acid and extracted withethyl acetate (10 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a colorless viscous substance ofN-ethyl-5-cyclopropyl-3-(2,6-dichloro-4-trifluoromethylpheyloxy)pyrazole-1-carboxamide(0.54 g, yield: 88.2%). ¹H-NMR (CDCl₃, TMS, ppm): δ 0.70 (m, 2H), 1.07(m, 2H), 1.20 (t, J=7.3 Hz, 3H), 2.81 (m, 1H), 3.36 (dq, J=6.0 and 7.3Hz, 2H), 5.45 (s, 1H), 6.60-6.85 (m, 1H), 7.66 (s, 2H).

Examples 167-171

Reactions of 3-(substituted phenyloxy)pyrazole derivatives (Example 167:3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-isopropylpyrazole, Example168: 5-tert-butyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)pyrazole,Example 169:3-(2,6-dichloro-4-trifluoromethylphenyloxy)-4-ethyl-5-methylpyrazole,Example 170:3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methoxymethylpyrazole,Example 171:{3-(2,6-dichloro-4-trifluoromethylphenyloxy)pyrazol-5-yl}acetate) withethyl isocyanate were carried out in the presence of a base in the samemanner as in Example 166, to give corresponding N-substitutedcarboxamides. Products/forms/yields/melting points/NMR spectra aredescribed below.

Example 167

N-ethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-isopropylpyrazole-1-carboxamide/whitesolid/yield: 21.9%/mp: 74-76° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.19 (t,J=7.3 Hz, 3H), 1.28 (d, J=6.8 Hz, 6H), 3.34 (dq, J=6.0 and 7.3 Hz, 2H),3.85 (sep, J=6.8 Hz, 1H), 5.77 (m, 1H), 6.77 (br t, J=6.0 Hz, 1H), 7.67(d, 0.4 Hz, 2H).

Example 168

N-ethyl-5-tert-butyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamide/colorlessviscous substance/yield: 31.4%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.18 (t,J=7.2 Hz, 3H), 1.46 (s, 9H), 3.33 (dq, J=5.9 and 7.2 Hz, 2H), 5.79 (s,1H), 6.80-6.95 (m, 1H), 7.67 (d, J=0.4 Hz, 2H).

Example 169

N-ethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-4-ethyl-5-methylpyrazole-1-carboxamide/whitesolid/yield: 27.6%/mp: 120-123° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.15 (t,J=7.5 Hz, 3H), 1.19 (t, J=6.3 Hz, 3H), 1.93 (s, 3H), 2.39 (q, J=7.5 Hz,2H), 3.29 (dq, J=6.0 and 6.3 Hz, 2H), 7.63 (s, 2H), 8.85 (br t, J=6.0Hz, 1H).

Example 170

N-ethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methoxymethylpyrazole-1-carboxamide/whitesolid/yield: 76.0%/mp: 106-108° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.20 (t,J=7.2 Hz, 3H), 3.35 (dq, J=6.0 and 7.2 Hz, 2H), 3.49 (s, 3H), 4.83 (d,J=1.0 Hz, 2H), 5.99 (t, J=1.0 Hz, 1H), 6.60-6.80 (m, 1H), 7.67 (d, J=0.4Hz, 2H).

Example 171

N-ethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-ethoxycarbonylmethylpyrazole-1-carboxamide/whitesolid/yield: 26.9%/mp: 100-102° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.18 (t,J=7.3 Hz, 3H), 1.27 (t, J=7.2 Hz, 3H), 3.33 (dq, J=6.0 and 7.3 Hz, 2H),4.04 (s, 2H), 4.20 (q, J=7.2 Hz, 2H), 5.94 (s, 1H), 6.60-6.80 (m, 1H),7.67 (d, J=0.5 Hz, 2H).

Example 172

Potassium carbonate (0.58 g, 4.2 mmol) and methyl isocyanate (0.20 g,3.5 mmol) were added to a solution of3-(2-nitro-4-trifluoromethylphenyloxy)-5-trifluoromethylpyrazole (1.43g, 4.2 mmol) in ethyl acetate (15 ml), and the mixture was stirred atroom temperature overnight. After completion of the reaction, thereaction mixture was poured into 2N hydrochloric acid and extracted withethyl acetate (10 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column (ethylacetate/hexane=1/5→1/1), to give a yellowish solid ofN-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)-5-trifluoromethylpyrazole-1-carboxamide(0.70 g, yield: 50.4%). mp: 102-104° C./¹H-NMR (CDCl₃, TMS, ppm): δ 3.53(s, 3H), 5.63 (s, 1H), 7.56 (d, J=8.3 Hz, 1H), 7.95 (d, J=8.3 Hz, 1H),8.39 (s, 1H), 10.05-10.75 (m, 1H).

Example 173

Potassium carbonate (0.69 g, 5.0 mmol) and ethyl isocyanate (0.28 g, 5.0mmol) were added to a solution of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-trifluoromethylpyrazole(1.66 g, 5.0 mmol) in ethyl acetate (20 ml), and the mixture was stirredat room temperature for 3 hours. After completion of the reaction, thereaction mixture was poured into 2N hydrochloric acid and extracted withethyl acetate (20 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column (ethylacetate/hexane=1/5→1/1), to give a white solid ofN-ethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-trifluoromethylpyrazole-1-carboxamide(0.83 g, yield: 51.6%). mp: 52-54° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.34(t, J=7.1 Hz, 3H), 3.75-4.30 (m, 2H), 5.66 (s, 1H), 7.98 (d, J=1.5 Hz,1H), 8.64 (m, 1H), 10.20-10.40 (m, 1H).

Example 174

Reaction of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-trifluoromethylpyrazolewith methyl isocyanate was carried out in the same manner as in Example173, to give a white solid ofN-methyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-trifluoromethylpyrazole-1-carboxamide(0.39 g, yield: 20.1%). mp: 61-63° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 3.52(s, 3H), 5.66 (s, 1H), 8.00 (d, J=11.8 Hz, 1H), 8.61 (d, J=1.8 Hz, 1H),10.10-10.40 (m, 1H).

Example 175

Triethylamine (0.20 g, 2.0 mmol) and ethyl isocyanate (0.14 g, 2.0 mmol)were added to a solution of methyl3-(2,6-dichloro-4-trifluoromethylphenyloxy)pyrazole-5-carboxylate (0.53g, 1.5 mmol) in ethyl acetate (10 ml), and the mixture was stirred atroom temperature for 6 hours. After completion of the reaction, thereaction mixture was poured into 2N hydrochloric acid and extracted withethyl acetate (10 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column(chloroform), to give a white solid of methyl3-(2,6-dichloro-4-trifluoromethylphenyloxy)-1(N-ethylcarbamoyl)pyrazole-5-carboxylate (0.15 g, yield: 23.5%). mp:88-90° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.20 (t, J=7.3 Hz, 3H), 3.37 (dq,J=6.0 and 7.3 Hz, 2H), 3.95 (s, 3H), 6.21 (s, 1H), 6.40-6.60 (m, 1H),7.68 (d, J=0.5 Hz, 2H).

Example 176

Potassium carbonate (0.25 g, 1.8 mmol) and ethyl isocyanate (0.11 g, 1.5mmol) were added to a solution of5-(4-chlorophenyl)-3-(2,6-dichloro-4-trifluoromethylphenyloxy)pyrazole(0.61 g, 1.5 mmol) in ethyl acetate (10 ml), and the mixture was stirredat room temperature overnight. After completion of the reaction, thereaction mixture was poured into 2N hydrochloric acid and extracted withethyl acetate (10 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column (ethylacetate/hexane=1/7), to give a white solid ofN-ethyl-5-(4-chlorophenyl)-3-(2,6-dichloro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.39 g, yield: 54.3%). mp: 88-89° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.17(t, J=7.3 Hz, 3H), 3.30 (dq, J=6.1 and 7.3 Hz, 2H), 5.96 (s, 1H),6.65-6.85 (m, 1H), 7.30-7.50 (m, 4H), 7.70 (s, 2H).

Example 177

Potassium carbonate (0.23 g, 1.7 mmol) and methoxymethyl isothiocyanate(0.15 g, 1.5 mmol) were added to a solution of3-(4-cyano-2-trifluoromethylphenyloxy)-5-methylpyrazole (0.40 g, 1.5mmol) in ethyl acetate (10 ml), and the mixture was stirred at roomtemperature overnight. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-methoxymethyl-3-(4-cyano-2-trifluoromethylphenyloxy)-5-methylpyrazole-1-carbothioamide(0.18 g, yield: 32.4%) mp: 89-90° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.84(s, 3H), 3.44 (s, 3H), 5.13 (d, J=6.2 Hz, 2H), 5.98 (m, 1H), 7.44 (d,J=8.7 Hz, 1H), 7.84 (dd, J=2.0 and 8.7 Hz, 1H), 8.01 (d, J=2.0 Hz, 1H),8.95-9.30 (m, 1H).

Example 178

Potassium carbonate (0.23 g, 1.7 mmol) and methoxymethyl isothiocyanate(0.16 g, 1.5 mmol) were added to a solution of3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole (0.47 g,1.5 mmol) in ethyl acetate (10 ml), and the mixture was stirred at roomtemperature overnight. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-methoxymethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carbothioamide(0.29 g, yield: 46.7%). mp: 95-96° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.82(d, J=0.6 Hz, 3H), 3.41 (s, 3H), 5.10 (d, J=6.3 Hz, 2H), 5.91 (q, J=0.6Hz, 1H), 7.68 (s, 2H), 8.80-9.20 (m, 1H).

Examples 179-185

Reactions of3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole withisothiocyanates (Examples 179: methyl isothiocyanate, Example 180: ethylisothiocyanate, Example 181: propyl isothiocyanate, Example 182:isopropyl isothiocyanate, Example 183: butyl isothiocyanate, Example184: 2-methoxyethyl isothiocyanate, Example 185: tetrahydrofurfurylisothiocyanate) were carried out in the same manner as in Example 178,to give corresponding N-substituted carbothioamides.Products/forms/yields/melting points/NMR spectra are described below.

Example 179

N-methyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carbothioamide/whitesolid/yield: 39.9%/mp: 121-123° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.82 (d,J=0.8 Hz, 3H), 3.15 (d, J=5.0 Hz, 3H), 5.86 (q, J=0.8 Hz, 1H), 7.67 (s,2H), 8.40-8.70 (m, 1H).

Example 180

N-ethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carbothioamide/whitesolid/yield: 29.8%/mp: 94-96° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.25 (t,J=7.5 Hz, 3H), 2.81 (s, 3H), 3.67 (dq, J=6.3 and 7.5 Hz, 2H), 5.78 (s,1H), 7.67 (s, 2H), 8.40-8.70 (m, 1H).

Example 181

N-propyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carbothioamide/whitesolid/yield: 22.7%/mp: 71-73° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.93 (t,J=7.3 Hz, 3H), 1.66 (tq, J=7.3 and 7.3 Hz, 2H), 2.81 (s, 3H), 3.57 (dt,J=6.0 and 7.3 Hz, 2H), 5.79 (s, 1H), 7.67 (s, 2H), 8.45-8.75 (m, 1H).

Example 182

N-isopropyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carbothioamide/whitesolid/yield: 9.7%/mp: 92-94° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.27 (d,J=6.5 Hz, 6H), 2.80 (s, 3H), 4.52 (m, 1H), 5.69 (s, 1H), 7.68 (s, 2H),8.20-8.70 (m, 1H).

Example 183

N-butyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carbothioamide/colorlessviscous substance/yield: 20.3%/¹H-NMR (CDCl₃, TMS, ppm): δ 0.92 (t,J=7.3 Hz, 3H), 1.25-1.80 (m, 4H), 2.81 (d, J=0.6 Hz, 3H), 3.61 (dt,J=5.7 and 7.2 Hz, 2H), 5.80 (q, J=0.6 Hz, 1H), 7.67 (s, 2H), 8.45-8.75(m, 1H).

Example 184

N-(2-methoxyethyl)-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carbothioamide/whitesolid/yield: 46.7%/mp: 83-86° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.81 (d,J=0.5 Hz, 3H), 3.29 (s, 3H), 3.56 (t, J=5.3 Hz, 2H), 3.81 (dt, J=5.3 and5.3 Hz, 2H), 5.84 (q, J=0.5 Hz, 1H), 7.67 (d, J=0.3 Hz, 2H), 8.65-9.00(m, 1H).

Example 185

N-tetrahydrofurfuryl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carbothioamide/whitesolid/yield: 16.5%/mp: 69-71° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.50-1.65(m, 1H), 1.65-2.05 (m, 3H), (s, 3H), 3.55-3.70 (m, 2H), 3.70-3.80 (m,2H), 4.05-4.20 (m, 1H), 5.86 (q, J=0.8 Hz, 1H), 7.66 (d, J=0.5 Hz, 2H),8.77 (br s, 1H).

Example 186

Potassium carbonate (0.22 g, 1.6 mmol) and ethyl isothiocyanate (0.13 g,1.8 mmol) were added to a solution of3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole (0.44g, 1.5 mmol) in ethyl acetate (10 ml), and the mixture was stirred atroom temperature overnight. After completion of the reaction, thereaction mixture was poured into 2N hydrochloric acid and extracted withethyl acetate (10 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-ethyl-3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carbothioamide(0.05 g, yield: 9.4%). mp: 114-115° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.25(t, J=7.3 Hz, 3H), 2.81 (d, J=0.6 Hz, 3H), 3.67 (dq, J=5.7 and 7.3 Hz,2H), 5.84 (q, J=0.6 Hz, 1H), 7.41 (dd, J_(HF)=2.1 and 9.4 Hz, 1H), 7.62(s, 1H), 8.54 (br s, 1H).

Example 187

Potassium carbonate (0.75 g, 5.4 mmol) and methyl isothiocyanate (0.39g, 5.4 mmol) were added to a solution of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole (1.00 g,3.6 mmol) in DMF (10 ml), and the mixture was stirred at roomtemperature for 8 hours. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-methyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carbothioamide(0.35 g, yield: 37.7%) mp: 63-65° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.87(d, J=0.6 Hz, 3H), 3.21 (d, J=4.9 Hz, 3H), 6.14 (q, J=0.6 Hz, 1H), 8.02(d, J=2.1 Hz, 1H), 8.36 (m, 1H), 8.80-9.05 (m, 1H).

Examples 188-196

Reactions of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole withisothiocyanates (Example 188: ethyl isothiocyanate, Example 189: propylisothiocyanate, Example 190: isopropyl isothiocyanate, Example 191:butyl isothiocyanate, Example 192: allyl isothiocyanate, Example 193:2-methoxymethyl isothiocyanate, Example 194: 2-methoxyethylisothiocyanate, Example 195: methyl 2-isothiocyanato-3-methylbutanoate,Example 196: 4-chlorobenzyl isothiocyanate) were carried out in the samemanner as in Example 187, to give corresponding N-substitutedcarbothioamides. Products/forms/yields/melting points/NMR spectra aredescribed below.

Example 188

N-ethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carbothioamide/whitesolid/yield: 11.2%/mp: 74-75° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.31 (t,J=7.3 Hz, 3H), 2.87 (s, 3H), 3.72 (dq, J=5.5 and 7.3 Hz, 2H), 6.13 (s,1H), 8.03 (d, J=2.0 Hz, 1H), 8.36 (m, 1H), 8.70-9.05 (m, 1H).

Example 189

N-propyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carbothioamide/whitesolid/yield: 6.4%/mp: 51-53° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.00 (t,J=7.3 Hz, 3H), 1.71 (tq, J=7.3 and 7.3 Hz, 2H), 2.87 (d, J=0.8 Hz, 3H),3.64 (dt, J=5.8 and 7.3 Hz, 2H), 6.13 (q, J=0.8 Hz, 1H), 8.02 (d, J=2.0Hz, 1H), 8.36 (m, 1H), 8.80-9.05 (m, 1H).

Example 190

N-isopropyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carbothioamide/colorlessviscous substance/yield: 5.4%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.32 (d, J=6.6Hz, 6H), 2.87 (d, J=0.5 Hz, 3H), 4.50-4.70 (m, 1H), 6.12 (m, 1H), 8.03(d, J=2.0 Hz, 1H), 8.36 (m, 1H), 8.60-8.85 (m, 1H).

Example 191

N-butyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carbothioamide/colorlessviscous substance/yield: 29.7%/¹H-NMR (CDCl₃, TMS, ppm): δ 0.96 (t,J=7.3 Hz, 3H), 1.30-1.55 (m, 2H), 1.68-1.80 (m, 2H), 2.87 (s, 3H),3.60-3.85 (m, 2H), 6.12 (s, 1H), 8.02 (d, J=1.8 Hz, 1H), 8.36 (m, 1H),8.75-9.05 (m, 1H).

Example 192

N-allyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carbothioamide/whitesolid/yield: 5.9%/mp: 46-48° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.87 (s,3H), 4.25-4.40 (m, 2H), 5.25-5.35 (m, 2H), 5.80-6.10 (m, 1H), 6.15 (q,J=0.5 Hz, 1H), 8.02 (d, J=2.0 Hz, 1H), 8.36 (m, 1H), 8.85-9.10 (m, 1H).

Example 193

N-(2-methoxymethyl)-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carbothioamide/whitesolid/yield: 31.3%/mp: 102-104° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.87 (s,3H), 3.44 (s, 3H), 5.16 (d, J=6.2 Hz, 2H), 6.18 (d, J=0.4 Hz, 1H), 8.04(d, J=2.1 Hz, 1H), 8.37 (m, 1H), 9.15-9.55 (m, 1H).

Example 194

N-(2-methoxyethyl)-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carbothioamide/whitesolid/yield: 16.1%/mp: 108-109° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.86 (d,J=0.6 Hz, 3H), 3.38 (s, 3H), 3.63 (t, J=5.4 Hz, 2H), 3.90 (dt, J=5.2 and5.4 Hz, 2H), 6.12 (q, J=0.6 Hz, 1H), 8.03 (d, J=1.8 Hz, 1H), 8.36 (m,1H), 9.00-9.25 (m, 1H).

Example 195

methyl2-[{3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazol-1-yl}thiocarbonylamino]-3-methylbutanoate/whitesolid/yield: 7.1%/mp: 109-110° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.95-1.15(m, 6H), 2.25-2.55 (m, 1H), 2.84 (m, 3H), 3.78 (s, 3H), 5.01 (dd, J=5.2and 8.3 Hz, 1H), 6.14 (q, J=0.5 Hz, 1H), 8.03 (d, J=2.1 Hz, 1H), 8.36(m, 1H), 9.10-9.40 (m, 1H).

Example 196

N-(4-chlorobenzyl)-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carbothioamide/whitesolid/yield: 12.2%/mp: 119-121° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.88 (d,J=0.5 Hz, 3H), 4.86 (d, J=5.3 Hz, 2H), 6.16 (s, 1H), 7.25-7.35 (m, 4H),8.01 (d, J=2.0 Hz, 1H), 8.34 (m, 1H), 9.05-9.30 (m, 1H).

Example 197

Potassium carbonate (0.76 g, 5.5 mmol) and 2-bromoethyl isothiocyanate(0.83 g, 5 mmol) were added to a solution of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole (1.39 g,5.0 mmol) in DMF (15 ml), and the mixture was stirred at roomtemperature for 3 hours. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid (30 ml) and extracted withethyl acetate (30 ml×3). An organic layer was washed with water, driedover anhydrous magnesium sulfate and filtered to remove a desiccant, andthe solvent was distilled off from the filtrate under reduced pressure.The resultant crude product was purified with a silica gel column (ethylacetate/hexane=1/20→1/10), to give a white solid ofN-vinyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carbothioamide(0.11 g, yield: 5.0%). mp: 90-92° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.87(d, J=0.8 Hz, 3H), 4.79 (d, J=8.6 Hz, 1H), 5.00 (dd, J=0.9 and 15.7 Hz,1H), 6.19 (q, J=0.8 Hz, 1H), 7.45 (ddd, J=0.9, 8.6 and 15.7 Hz, 1H),8.04 (d, J=2.1 Hz, 1H), 8.36 (m, 1H), 10.15-10.55 (m, 1H).

Example 198

Trichloromethyl chloroformate (0.59 g, 3.0 mmol) was added to a solutionof 5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole (0.48 g, 2.0 mmol) inethyl acetate (10 ml) at 0° C., and while the mixture was allowed tohave room temperature gradually, the mixture was further stirred at roomtemperature for 3 hours. To the reaction mixture were addedO-ethylhydroxylamine hydrochloride (0.98 g, 10.0 mmol) and triethylamine(0.61 g, 6.0 mmol), and the resulting mixture was refluxed underheating. After completion of the reaction, the reaction mixture waspoured into ice water, and the mixture was extracted with ethyl acetate(20 ml×3). An organic layer was washed with water, dried over anhydrousmagnesium sulfate and filtered to remove a desiccant, and the solventwas distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a yellowish viscous substance ofN-ethoxy-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.30 g, yield: 45.4%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.31 (t, J=7.0 Hz,3H), 2.61 (d, J=0.8 Hz, 3H), 4.05 (q, J=7.0 Hz, 2H), 5.78 (q, J=0.8 Hz,1H), 7.33-7.37 (m, 1H), 7.42-7.50 (m, 3H), 9.25 (br s, 1H).

Example 199

5-Methyl-3-(3-trifluoromethylphenyloxy)pyrazole reacted withtrichloromethyl chloroformate in the same manner as in Example 198 andthen reacted with tetrahydrofurfurylamine to give a white solid ofN-tetrahydrofurfuryl-5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide(yield: 70.3%). mp: 101-102° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.56-1.67(m, 1H), 1.84-2.05 (m, 3H), 2.60 (s, 3H), 3.29-3.39 (m, 1H), 3.55 (ddd,J=3.8, 6.1 and 13.8 Hz, 1H), 3.70-3.90 (m, 2H), 4.00-4.10 (m, 1H), 5.74(s, 1H), 7.21 (br s, 1H), 7.33-7.37 (m, 1H), 7.40-7.51 (m, 3H).

Example 200

Trichloromethyl chloroformate (0.58 g, 3.0 mmol) was added to a solutionof 3-(4-chloro-2-trifluoromethylphenyloxy)-5-methylpyrazole (0.55 g, 2.0mmol) in ethyl acetate (10 ml) at 0° C., and the mixture was furtherstirred at an ambient temperature for 30 minutes. Then, the mixture wasrefluxed under heating for 1 hour. The solvent was distilled off fromthe reaction mixture and then the reaction mixture was cooled to 0° C.and dissolved in toluene (10 ml). Triethylamine (0.61 g, 6.0 mmol) andtetrahydrofurfurylamine (1.01 g, 10.0 mmol) were added, and while themixture was allowed to have room temperature gradually, it was stirredfor 1 hour. Then, the mixture was refluxed under heating for 2 hours.After completion of the reaction, the reaction mixture was poured into1N hydrochloric acid (10 ml), and the mixture was extracted with ethylacetate (10 ml×2). An organic layer was washed with water (10 ml×3),dried over anhydrous magnesium sulfate and filtered to remove adesiccant, and the solvent was distilled off from the filtrate underreduced pressure. The resultant crude product was purified with a silicagel column (ethyl acetate/hexane=1/10), to give a colorless viscoussubstance ofN-tetrahydrofurfuryl-3-(4-chloro-2-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.40 g, yield: 48.9%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.55-1.66 (m, 1H),1.84-2.02 (m, 3H), 2.59 (d, J=0.8 Hz, 3H), 3.26-3.37 (m, 1H), 3.54 (ddd,J=3.7, 6.2 and 13.8 Hz, 1H), 3.71-3.90 (m, 2H), 4.00-4.16 (m, 1H), 5.74(q, J=0.8 Hz, 1H), 7.18 (br s, 1H), 7.25 (d, J=8.7 Hz, 1H), 7.48 (dd,J=2.5 and 8.7 Hz, 1H), 7.64 (d, J=2.5 Hz, 1H).

Example 201

Trichloromethyl chloroformate (0.59 g, 3.0 mmol) was added to a solutionof 3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole (0.83 g,3.0 mmol) in chloroform (10 ml) at 0° C., and while the mixture wasallowed to have room temperature gradually, it was further stirred atroom temperature for 3 hours. Cyclopropylamine (0.17 g, 3.0 mmol) andpotassium carbonate (0.50 g, 3.6 mmol) were added to the reactionmixture, and the reaction mixture was refluxed under heating for 5hours. After completion of the reaction, the reaction mixture was pouredinto ice water and extracted with chloroform (20 ml×3). An organic layerwas washed with water, dried over anhydrous magnesium sulfate andfiltered to remove a desiccant, and the solvent was distilled off fromthe filtrate under reduced pressure. The resultant crude product waspurified with a silica gel column (ethyl acetate/hexane=1/7), to give acolorless viscous substance ofN-cyclopropyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.27 g, yield: 22.8%). ¹H-NMR (CDCl₃, TMS, ppm): δ 0.55-0.65 (m, 2H),0.75-0.85 (m, 2H), 2.59 (d, J=0.4 Hz, 3H), 2.60-2.75 (m, 1H), 5.71 (m,1H), 6.75-6.90 (m, 1H), 7.67 (s, 2H).

Examples 202-216

3-(2,6-Dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole reactedwith trichloromethyl chloroformate, and then reacted with amines(Example 202: s-butylamine, Example 203: 3-aminopentane, Example 204:cyclopentylamine, Example 205: propargylamine, Example 206:O-ethylhydroxylamine hydrochloride, Example 207:O-tert-butylhydroxylamine, Example 208: O-allylhydroxylamine, Example209: O-benzylhydroxylamine, Example 210: ethanolamine, Example 211:2,2,2-trifluoroethylamine, Example 212: tetrahydrofurfurylamine, Example213: furfurylamine, Example 214: 2-morpholinoethylamine, Example 215:2-picolylamine, Example 216: 2-thienylmethylamine) in the same manner asin Example 201, to give N-substituted carboxamides.Products/forms/yields/melting points/NMR spectra are described below.

Example 202

N-s-butyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 48.8%/mp: 73-75° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.92 (t,J=7.5 Hz, 3H), 1.19 (d, J=6.7 Hz, 3H), 1.45-1.60 (m, 2H), 2.57 (d, J=0.7Hz, 3H), 3.82 (dq, J=6.7 and 8.4 Hz, 1H), 5.62 (d, J=0.7 Hz, 1H), 6.62(br d, J=8.4 Hz, 1H), 7.57 (s, 2H).

Example 203

N-(3-pentyl)-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 43.6%/mp: 65-67° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.91 (t,J=7.4 Hz, 6H), 1.53 (m, 4H), 2.58 (s, 3H), 3.67 (m, 1H), 5.63 (s, 1H),6.58 (br d, J=9.0 Hz, 1H), 7.67 (s, 2H).

Example 204

N-cyclopentyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 47.4%/mp: 90-92° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.35-1.80(m, 6H), 1.90-2.10 (m, 2H), 2.57 (d, J=0.4 Hz, 3H), 4.13 (dt, J=7.0 and7.0 Hz, 1H), 5.61 (d, J=0.6 Hz, 1H), 6.72 (br d, J=7.0 Hz, 1H), 7.67 (s,2H).

Example 205

N-propargyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substance/yield: 21.7%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.25 (t,J=2.5 Hz, 1H), 2.59 (s, 3H), 4.09 (dd, J=2.5 and 6.0 Hz, 2H), 5.78 (s,1H), 6.85-7.00 (m, 1H), 7.67 (s, 2H).

Example 206

N-ethoxy-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 5.0%/mp: 105-107° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.28 (t,J=7.1 Hz, 3H), 2.59 (s, 3H), 4.03 (q, J=7.1 Hz, 2H), 5.82 (s, 1H), 7.67(s, 2H), 9.05 (s, 1H).

Example 207

N-t-butoxy-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 40.7%/mp: 92-94° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.29 (s,9H), 2.58 (d, J=0.8 Hz, 3H), 5.76 (q, J=0.8 Hz, 1H), 7.67 (s, 2H), 8.73(s, 1H).

Example 208

N-allyloxy-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 37.8%/mp: 68-70° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.59 (d,J=0.8 Hz, 3H), 4.35-4.50 (m, 2H), 5.20-5.45 (m, 2H), 5.82 (d, J=0.8 Hz,1H), 5.85-6.10 (m, 1H), 7.67 (d, J=0.4 Hz, 2H), 9.06 (br s, 1H).

Example 209

N-benzyloxy-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 26.1%/mp: 98-100° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.61 (d,J=0.7 Hz, 3H), 4.95 (s, 2H), 5.83 (q, J=0.9 Hz, 1H), 7.30-7.45 (m, 5H),7.63 (d, J=0.5 Hz, 2H), 9.00 (br s, 1H).

Example 210

N-(2-hydroxyethyl)-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 20.1%/mp: 124-126° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.25 (m,1H), 2.58 (s, 3H), 3.40-3.55 (m, 2H), 3.70-3.85 (m, 2H), 5.76 (q, J=0.5Hz, 1H), 6.90-7.15 (m, 1H), 7.66 (s, 2H).

Example 211

N-2,2,2-trifluoroethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 51.6%/mp: 104-106° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.60 (d,J=0.5 Hz, 3H), 3.93 (dq, J=6.8 and 8.8 Hz, 2H), 5.80 (q, J=0.7 Hz, 1H),7.05 (br t, J=6.8 Hz, 1H), 7.68 (s, 2H).

Example 212

N-tetrahydrofurfuryl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 13.7%/mp: 74-76° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.45-1.65(m, 1H), 1.75-2.05 (m, 3H), 2.58 (d, J=0.8 Hz, 3H), 3.32 (dt, J=6.2 and13.9 Hz, 1H), 3.47 (ddd, J=3.7, 5.6 and 13.9 Hz, 1H), 3.60-3.85 (m, 2H),3.95-4.15 (m, 1H), 5.75 (q, J=0.8 Hz, 1H), 6.85-7.15 (m, 1H), 7.66 (s,2H).

Example 213

N-furfuryl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/orangeviscous substance/yield: 24.0%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.59 (d,J=0.6 Hz, 3H), 4.47 (d, J=6.0 Hz, 2H), 5.73 (q, J=0.8 Hz, 1H), 6.25 (m,1H), 6.32 (dd, J=1.8 and 3.2 Hz, 1H), 7.07 (br t, J=6.0 Hz, 1H), 7.35(dd, J=0.8 and 1.8 Hz, 1H), 7.66 (s, 2H).

Example 214

N-(2-morpholinoethyl)-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 25.7%/mp: 99-101° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.40 (t,J=4.7 Hz, 4H), 2.50 (t, J=6.2 Hz, 2H), 2.59 (d, J=0.8 Hz, 3H), 3.37 (dt,J=5.4 and 6.1 Hz, 2H), 3.57 (t, J=4.7 Hz, 4H), 5.80 (q, J=0.8 Hz, 1H),7.10-7.25 (m, 1H), 7.67 (s, 2H).

Example 215

N-2-picolyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 27.0%/mp: 121-123° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.60 (d,J=0.8 Hz, 3H), 4.59 (d, J=5.8 Hz, 2H), 5.77 (q, J=0.8 Hz, 1H), 7.19 (dd,J=5.8 and 7.8 Hz, 1H), 7.31 (d, J=7.8 Hz, 1H), 7.55-7.70 (m, 4H), 8.50(d, J=4.2 Hz, 1H).

Example 216

N-(2-thienylmethyl)-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/yellowviscous substance/yield: 34.1%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.61 (d,J=0.8 Hz, 3H), 4.65 (d, J=5.9 Hz, 2H), 5.74 (q, J=0.8 Hz, 1H), 6.90-7.05(m, 2H), 7.05-7.20 (m, 1H), 7.20-7.30 (m, 1H), 7.66 (s, 2H).

Example 217

Trichloromethyl chloroformate (0.39 g, 2.0 mmol) was added to a solutionof 3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole(0.59 g, 2.0 mmol) in chloroform (10 ml) at 0° C., and while the mixturewas allowed to have room temperature gradually, it was further stirredat room temperature for 3 hours. Tetrahydrofurfurylamine (0.61 g, 6.0mmol) and triethylamine (0.4 g, 4.0 mmol) were added to the reactionmixture, the reaction mixture was refluxed under heating for 5 hours.After completion of the reaction, the reaction mixture was poured intoice water and extracted with chloroform (20 ml×3). An organic layer waswashed with water, dried over anhydrous magnesium sulfate and filteredto remove a desiccant, and the solvent was distilled off from thefiltrate under reduced pressure. The resultant crude product waspurified with a silica gel column (ethyl acetate/hexane=1/10→1/5), togive a colorless viscous substance ofN-tetrahydrofurfuryl-3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.25 g, yield: 29.6%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.50-1.65 (m, 1H),1.75-2.05 (m, 3H), 2.58 (s, 3H), 3.32 (dt, J=6.3 and 13.9 Hz, 1H), 3.48(ddd, J=3.7, 5.7 and 13.9 Hz, 1H), 3.74 (dq, J=7.0 and 8.6 Hz, 2H), 4.03(dq, J=3.7 and 7.0 Hz, 1H), 5.79 (s, 1H), 6.85-7.10 (m, 1H), 7.39 (dd,J_(HF)=1.9 and 9.3 Hz, 1H), 7.56 (s, 1H).

Example 218

Trichloromethyl chloroformate (0.49 g, 2.5 mmol) was added to a solutionof 3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole (0.69g, 2.5 mmol) in chloroform (10 ml) at 0° C., and while the mixture wasallowed to have room temperature gradually, it was further stirred atroom temperature for 3 hours. Sec-butylamine (0.22 g, 3.0 mmol) andpotassium carbonate (0.42 g, 3.0 mmol) were added to the reactionmixture, and the mixture was stirred at 50° C. for 8 hours. Aftercompletion of the reaction, the reaction mixture was poured into icewater and extracted with chloroform (20 ml×3). An organic layer waswashed with water, dried over anhydrous magnesium sulfate and filteredto remove a desiccant, and the solvent was distilled off from thefiltrate under reduced pressure. The resultant crude product waspurified with a silica gel column (ethyl acetate/hexane=1/7), to give acolorless viscous substance ofN-s-butyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide(0.24 g, yield: 25.5%). ¹H-NMR (CDCl₃, TMS, ppm): δ 0.96 (t, J=7.5 Hz,3H), 1.22 (d, J=6.6 Hz, 3H), 1.45-1.65 (m, 2H), 2.65 (s, 3H), 3.75-4.00(m, 1H), 6.04 (s, 1H), 6.75-7.05 (m, 1H), 8.02 (d, J=1.8 Hz, 1H),8.30-8.40 (m, 1H).

Examples 219-222

3-(3-Chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole reactedwith trichloromethyl chloroformate, and then reacted with amines(Example 219: cyclopropylamine, Example 220: isobutylamine, Example 221:O-methylhydroxylamine hydrochloride, Example 223: O-ethylhydroxylaminehydrochloride) in the same manner as in Example 218, to givecorresponding carboxamides. Products/forms/yields/melting points/NMRspectra are described below.

Example 219

N-cyclopropyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 37.9%/mp: 98-99° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.55-0.70(m, 2H), 0.75-0.90 (m, 2H), 2.66 (s, 3H), 2.70-2.85 (m, 1H), 6.05 (s,1H), 7.05-7.20 (m, 1H), 8.02 (d, J=2.1 Hz, 1H), 8.35 (d, J=2.1 Hz, 1H).

Example 220

N-isobutyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 29.7%/mp: 45-47° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.96 (d,J=6.7 Hz, 6H), 1.87 (sep, J=6.7 Hz, 1H), 2.65 (d, J=0.6 Hz, 3H), 3.18(t, J=6.5 Hz, 2H), 6.04 (q, J=0.6 Hz, 1H), 7.00-7.20 (m, 1H), 8.02 (d,J=2.1 Hz, 1H), 8.35 (m, 1H).

Example 221

N-methoxy-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/colorlessviscous substance/yield: 19.4%/¹H-NMR (CDCl₃, TMS, ppm): δ 2.66 (d,J=0.7 Hz, 3H), 3.86 (s, 3H), 6.10 (q, J=0.7 Hz, 1H), 8.03 (d, J=2.1 Hz,1H), 8.35 (m, 1H), 9.35-9.55 (m, 1H).

Example 222

N-ethoxy-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/yellowviscous substance/yield: 38.5%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.32 (t,J=7.0 Hz, 3H), 2.66 (s, 3H), 4.07 (q, J=7.0 Hz, 2H), 6.10 (s, 1H), 8.03(d, J=2.1 Hz, 1H), 8.35 (m, 1H), 9.38 (br s, 1H).

Example 223

Trichloromethyl chloroformate (3.0 g, 15.0 mmol) was added to a solutionof 3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole (4.67 g,15.0 mmol) in chloroform (50 ml) at 0° C., and while the mixture wasallowed to have room temperature gradually, it was further stirred atroom temperature for 4 hours. 30% ammonia solution (10 ml) was added tothe reaction mixture, and the mixture was further stirred at roomtemperature for 1 hour. After completion of the reaction, water wasadded to the reaction mixture, and the mixture was extracted with ethylacetate (30 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant, and thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/7), to give a white solid of3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(2.82 g, yield: 53.1%). mp: 152-154° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ2.58 (d, J=0.4 Hz, 3H), 4.80-5.15 (br s, 1H), 5.80 (q, J=0.4 Hz, 1H),6.45-6.80 (br s, 1H), 7.66 (s, 2H).

Examples 224-226

3-(Substituted phenyloxy)-5-methylpyrazoles (Example 224:3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole, Example225: 3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole,Example 226: 5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole) reactedwith trichloromethyl chloroformate, and then reacted with ammoniasolution in the same manner as in Example 223, to give correspondingcarboxamide derivatives. Products/forms/yields/melting points/NMRspectra are described below.

Example 224

3-(2-chloro-6-fluoro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 35.5%/mp: 132-135° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.59 (d,J=0.8 Hz, 3H), 4.75-5.20 (br s, 1H), 5.84 (q, J=0.8 Hz, 1H), 6.45-6.80(br s, 1H), 7.39 (dd, J_(HF)=2.0 and 9.3 Hz: 1H), 7.56 (s, 1H).

Example 225

3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 76.7%/mp: 101-104° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.65 (d,J=0.6 Hz, 3H), 5.00-5.40 (br s, 1H), 6.08 (m, 1H), 6.75-7.15 (br s, 1H),8.03 (d, J=2.1 Hz, 1H), 8.36 (m, 1H).

Example 226

5-methyl-3-(3-trifluoromethylphenyloxy)pyrazole-1-carboxamide/whitesolid/yield: 35.8%/mp: 76-77° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.60 (d,J=0.8 Hz, 3H), 5.09 (br s, 2H), 5.77 (q, J=0.8 Hz, 1H), 7.33-7.38 (m,1H), 7.41-7.52 (m, 3H).

Example 227

Trichloromethyl chloroformate (0.46 g, 2.3 mmol) was added to a solutionof 3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole (0.47 g,1.5 mmol) in ethyl acetate (10 ml) at 0° C., and while the mixture wasallowed to have room temperature gradually, it was further stirred underreflux for 4 hours. The reaction mixture was concentrated, and further,toluene (10 ml), triethylamine (0.46 g, 4.5 mmol) and pyrrolidine (0.43g, 6.0 mmol) were added. Further, the mixture was refluxed under heatingfor 3 hours. After completion of the reaction, water was added to thereaction mixture, and the mixture was extracted with ethyl acetate (50ml×3). An organic layer was washed with water, dried over anhydrousmagnesium sulfate and filtered to remove a desiccant, and the solventwas distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/5), to give a white solid ofN,N-tetramethylene-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.11 g, yield: 18.0%). mp: 102-104° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.70-1.95 (m, 4H), 2.50 (d, J=0.6 Hz, 3H), 3.40-3.60 (m, 4H), 5.78 (q,J=0.6 Hz, 1H), 7.64 (s, 2H).

Example 228

3-(2,6-Dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole reactedwith trichloromethyl chloroformate to obtain an intermediate, andfurther, the intermediate reacted with 2,6-dimethylmorpholine, in thesame manner as in Example 228, to give a white solid of3-(2,6-dichloro-4-trifluoromethylphenyloxy-1-(2,6-dimethylmorpholino)carbonyl-5-methylpyrazole(0.14 g, yield: 20.6%). mp: 87˜89° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ0.90-1.30 (m, 6H), 2.46 (d, J=0.7 Hz, 3H), 2.50-2.65 (m, 2H), 3.20-3.75(m, 2H), 3.80-4.25 (m, 2H), 5.85 (q, J=0.7 Hz, 1H), 7.64 (s, 2H).

Example 229

N-allyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(4.3 g, 10.9 mmol) was dissolved in a solution mixture of ether (50 ml)and water (50 ml), an aqueous solution (60 ml) of osmium tetraoxide (254mg, 1.0 mmol) and sodium periodate (4.7 g, 21.8 mmol) were added, andthe mixture was stirred at room temperature overnight. After completionof the reaction, a 10% sodium thiosulfate aqueous solution (100 ml) andethyl acetate (100 ml) were added to the reaction solution, and anorganic layer was separated and an aqueous layer was extracted withethyl acetate (50 ml×2). These organic layers combined were washed witha saturated sodium chloride aqueous solution, dried over anhydrousmagnesium sulfate and filtered to remove a desiccant. The solvent wasdistilled off from the filtrate under reduced pressure. The resultantcrude product was purified with a silica gel column (ethylacetate/hexane=1/7→1/5), to give a white solid ofN-formylmethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(2.12 g, yield: 49.1%). mp: 111-113° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ2.59 (d, J=0.8 Hz, 3H), 4.17 (d, J=5.5 Hz, 2H), 5.81 (q, J=0.8 Hz, 1H),7.21 (br t, J=5.5 Hz, 1H), 7.67 (s, 2H), 9.66 (s, 1H).

Example 230

p-Toluenesulfonic acid monohydrate (20 mg, 0.1 mmol) and ethylene glycol(0.31 g, 5 mmol) were added to a solution ofN-formylmethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.40 g, 1.0 mmol) in benzene (10 ml), and the mixture was refluxedunder heating for 5 hours. After completion of the reaction, the solventwas distilled off from the reaction mixture, water (30 ml) was added tothe residue, and the mixture was extracted with ethyl acetate (30 ml×3).An organic layer was washed with a saturated sodium chloride aqueoussolution, dried over anhydrous magnesium sulfate and filtered to removea desiccant. The solvent was distilled off from the filtrate underreduced pressure. The resultant crude product was purified with a silicagel column (ethyl acetate/hexane=1/7→chloroform), to give a white solidofN,N-(1,3-dioxa-2-cyclopentyl)methyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.33 g, yield: 75.0%). mp: 80-81° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.59(d, J=0.8 Hz, 3H), 3.53 (dd, J=3.3 and 6.1 Hz, 2H), 3.80-3.95 (m, 4H),5.03 (t, J=3.3 Hz, 1H), 5.76 (q, J=0.8 Hz, 1H), 6.92 (br t, J=6.1 Hz,1H), 7.66 (s, 2H).

Examples 231-232

N-Formylmethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamidereacted with alcohols (Example 231: 1,3-propanediol, Example 232:methanol) in the same manner as in Example 230, to give correspondingcarboxamides. Products/forms/yields/melting points/NMR spectra aredescribed below.

Example 231

N,N-(1,3-dioxa-2-cyclohexyl)methyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 74.9%/mp: 87-89° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.25-1.45(m, 1H), 1.95-2.15 (m, 1H), 2.58 (d, J=0.8 Hz, 3H), 3.41 (dd, J=4.7 and6.1 Hz, 2H), 3.65-3.85 (m, 1H), 4.00-4.15 (m, 1H), 4.67 (t, 4.7 Hz, 1H),5.73 (q, J=0.8 Hz, 1H), 6.90-7.10 (br t, J=6.1 Hz, 1H), 7.67 (s, 2H).

Example 232

N,N-2,2-dimethoxyethyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/mp: 57-59° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.58 (d, J=0.7 Hz, 3H),3.38 (s, 6H), 3.35-3.45 (m, 2H), 4.41 (t, J=5.4 Hz, 1H), 5.75 (q, J=0.8Hz, 1H), 6.80-7.00 (m, 1H), 7.66 (d, J=0.4 Hz, 2H).

Example 233

Potassium hydroxide (0.42 g, 7.5 mmol) and 30% hydrogen peroxide (2.7ml) were added to a solution ofN-butyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carbothioamide(0.98 g, 2.5 mmol) in methanol (10 ml), and the mixture was stirred atroom temperature for 3 hours. Concentrated hydrochloric acid was addedto the reaction mixture up to a pH of 1, and the mixture was furtherstirred at room temperature for 2 hours. After completion of thereaction, the reaction mixture was extracted with ethyl acetate (15ml×3), and the organic layer was washed with water, dried over anhydrousmagnesium sulfate and filtered to remove a desiccant. The solvent wasdistilled off from the filtrate under reduced pressure. The resultantcrude product was purified with a silica gel column (ethylacetate/hexane=1/10→1/1), to give a colorless viscous substance ofN-butyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide(0.17 g, yield: 18.1%). ¹H-NMR (CDCl₃, TMS, ppm): δ 0.94 (t, J=7.3 Hz,3H), 1.30-1.50 (m, 2H), 1.50-1.70 (m, 2H), 2.65 (s, 3H), 3.35 (dt, J=6.3and 6.3 Hz, 2H), 6.04 (s, 1H), 6.90-7.20 (m, 1H), 8.02 (d, J=2.0 Hz,1H), 8.35 (m, 1H).

Example 234

Potassium carbonate (0.07 g, 0.50 mmol) was added to a solution ofN-allyl-3-hydroxy-5-methylpyrazole-1-carboxamide (0.18 g, 1.0 mmol) inDMF (5 ml), then, 3,5-dichloro-4-fluorotrifluoromethylbenzene (0.23 g,1.0 mmol) was added, and the mixture was stirred at room temperature for5 hours. After completion of the reaction, the reaction mixture waspoured into 1N hydrochloric acid (10 ml), and the mixture was extractedwith ethyl acetate (10 ml×2). An organic layer was washed with water (10ml×3) and dried over anhydrous magnesium sulfate, and a desiccant wasremoved from a filtrate. The solvent was distilled off from the filtrateunder reduced pressure. The resultant crude product was purified with asilica gel column (ethyl acetate/hexane=1/10), to give a yellow viscoussubstance ofN-allyl-3-(2,6-dichloro-4-trifluoromethyloxy)-5-methylpyrazole-1-carboxamide(0.18 g, yield: 45.7%). The product had NMR spectrum as shown in Example112.

Example 235

Diethylcarbamoyl chloride (1.52 g, 7.8 mmol) was added to a solution of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole (1.39 g,5.0 mmol) and potassium carbonate (1.98 g, 14.3 mmol) in DMF (15 ml),the mixture was stirred at 70° C. for 9 hours and further stirred atroom temperature for 2 days. After completion of the reaction, thereaction mixture was poured into 2N hydrochloric acid, and the mixturewas extracted with ethyl acetate (20 ml×3). An organic-layer was washedwith water, dried over anhydrous magnesium sulfate and filtered toremove a desiccant. The solvent was distilled off from the filtrateunder reduced pressure. The resultant crude product was purified with asilica gel column (ethyl acetate/hexane=1/5), to give a colorlessviscous substance ofN,N-diethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide(0.21 g, yield: 11.2%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.21 (t, J=7.0 Hz,6H), 2.48 (d, J=0.6 Hz, 3H), 3.47 (q, J=7.0 Hz, 4H), 6.00 (q, J=0.6 Hz,1H), 7.99 (d, J=2.1 Hz, 1H), 8.33 (m, 1H).

Example 236

A solution of diisopropylcarbamoyl chloride (1.47 g, 9.0 mmol) inpyridine (5 ml) was added to a solution of3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole (1.67 g,6.0 mmol) in pyridine (10 ml), and the mixture was stirred under heatingat 80° C. for 20 hours. After completion of the reaction, the reactionmixture was poured into 2N hydrochloric acid, and the mixture wasextracted with ethyl acetate (20 ml×3). An organic layer was washed withwater, dried over anhydrous magnesium sulfate and filtered to remove adesiccant. The solvent was distilled off from the filtrate under reducedpressure. The resultant crude product was purified with a silica gelcolumn (ethyl acetate/hexane=1/5), to give a white solid ofN,N-diisopropyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide(2.1 g, yield: 86.7%). mp: 58-60° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.28(d, J=7.5 Hz, 12H), 2.29 (s, 3H), 3.50-4.10 (m, 2H), 6.00 (s, 1H), 7.98(d, J=2.5 Hz, 1H), 8.31 (m, 1H).

Example 237

N,N-Dimethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamidewas obtained in the same manner as in Example 235. White solid/yield:30.6%/mp: 102-104° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.32 (s, 3H),2.85-3.30 (br s, 6H), 6.01 (s, 1H), 7.99 (d, J=2.0 Hz, 1H), 8.30 (m,1H).

Examples 238-240

3-(3-Chloro-5-trifluoromethylpyridin-2-yloxy)-5-trifluoromethylpyrazolereacted with carbamoyl chloride derivatives (Example 238:dimethylcarbamoyl chloride, Example 240 diethylcarbamoyl chloride,Example 241: diisopropylcarbamoyl chloride) in the same manner as inExample 236, to give corresponding carboxamides.Products/forms/yields/melting points/NMR spectra are described below.

Example 238

N,N-dimethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-trifluoromethylpyrazole-1-carboxamide/orangeviscous substance/yield: 25.0%/¹H-NMR (CDCl₃, TMS, ppm): δ 3.13 (s, 6H),6.51 (s, 1H), 8.00-8.10 (m, 1H), 8.25-8.35 (m, 1H).

Example 239

N,N-diethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-trifluoromethylpyrazole-1-carboxamide/whitesolid/yield: 58.1%/mp: 58-60° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.27 (m,6H), 3.40 (q, J=6.9 Hz, 4H), 6.51 (s, 1H), 8.03 (d, J=2.1 Hz, 1H), 8.30(m, 1H).

Example 240

N,N-diisopropyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-trifluoromethylpyrazole-1-carboxamide/colorlessviscous substance/yield: 50.9%/¹H-NMR (CDCl₃, TMS, ppm): δ 1.10-1.55 (m,12H), 3.35-4.05 (m, 2H), 6.53 (s, 1H), 8.04 (d, J=2.2 Hz, 1H), 8.34 (m,1H).

Example 241

N,N-Diisopropyl-3-(2-nitro-4-trifluoromethylphenyloxy)-5-trifluoromethylpyrazole-1-carboxamidewas obtained in the same manner as in Example 236. White solid/yield:22.9%/mp: 118-120° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.33 (d, J=5.9 Hz,12H), 2.27 (s, 3H), 3.30-4.25 (m, 2H), 5.70 (s, 1H), 7.43 (d, J=8.8 Hz,1H), 7.78 (dd, J=2.0 and 8.8 Hz, 1H), 8.24 (d, J=2.0 Hz, 1H).

Example 242

A solution ofN-methyl-5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamide(2.1 g, 6.0 mmol) in ethanol (50 ml) was placed in an autoclave, and 10%palladium carbon (0.7 g) was added. An atmosphere in the autoclave wasfully replaced with hydrogen gas, and hydrogen gas was charged up to 5kg/cm². Then, the reaction solution was stirred at room temperature for5 hours. After completion of the reaction, the catalyst was removed byfiltration using Celite, and the solvent was distilled off from thefiltrate under reduced pressure, to give a yellowish solid ofN-methyl-3-(2-amino-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(1.6 g, yield: 82.2%). mp: 93-94; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.59 (d,J=0.7 Hz, 3H), 2.93 (d, J=5.0 Hz, 1H), 3.90-4.15 (br s, 2H), 5.71 (q,J=0.7 Hz, 1H), 6.80-6.95 (m, 1H), 6.97 (dd, J=1.7 and 8.4 Hz, 1H), 7.11(d, J=8.4 Hz, 1H).

Example 243

Sulfuryl chloride (0.24 g, 1.8 mmol) was added to a solution ofN-isopropyl-5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.56 g, 1.5 mmol) in acetic acid (5 ml), and the mixture was stirred atroom temperature for 4 hours. After completion of the reaction, thereaction mixture was poured into ice water and extracted with ethylacetate (20 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant. Thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a yellowish solid ofN-isopropyl-4-chloro-5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.60 g, yield: 98.4%). mp: 89-91° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.24(d, J=6.6 Hz, 6H), 2.63 (s, 3H), 3.90-4.10 (m, 1H), 6.40-6.65 (m, 1H),7.38 (d, J=8.7 Hz, 1H), 7.85 (dd, J=2.0 and 8.7 Hz, 1H), 8.29 (d, J=2.0Hz, 1H).

Example 244

A white solid ofN-methyl-4-chloro-5-methyl-3-(2-nitro-4-trifluoromethylphenyloxy)pyrazole-1-carboxamidewas obtained in the same manner as in Example 243 (0.36 g, yield:79.3%). mp: 107-108° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 2.63 (s, 3H), 2.91(d, J=5.0 Hz, 3H), 6.50-6.75 (m, 1H), 7.46 (d, J=8.7 Hz, 1H), 7.88 (dd,J=2.0 and 8.7 Hz, 1H), 8.30 (d, J=2.0 Hz, 1H).

Example 245

Sulfuryl chloride (0.16 g, 1.2 mmol) was added to a solution ofN-methyl-5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.34 g, 1.0 mmol) in acetic acid (5 ml), and the mixture was stirred atroom temperature for 4 hours. After completion of the reaction, thereaction mixture was poured into ice water and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant. Thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-methyl-4-chloro-5-methyl-3-(4-nitro-2-trifluoromethylphenyloxy)pyrazole-1-carboxamide(0.27 g, yield: 71.2%). mp: 157-158° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ2.66 (s, 3H), 2.96 (d, J=5.0 Hz, 3H), 6.70-6.95 (m, 1H), 7.31 (d, J=9.2Hz, 1H), 8.41 (dd, J=2.7 and 9.2 Hz, 1H), 8.62 (d, J=2.7 Hz, 1H).

Example 246

Sulfuryl chloride (0.16 g, 1.2 mmol) was added to a solution ofN-hexyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.44 g, 1.0 mmol) in acetic acid (5 ml), and the mixture was stirred atroom temperature for 4 hours. After completion of the reaction, thereaction mixture was poured into ice water and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant. Thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane 1/10), to give a white solid ofN-hexyl-4-chloro-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.40 g, yield: 84.8%). mp: 86-88° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 0.88(t, J=6.8 Hz, 3H), 1.26 (m, 6H), 1.40-1.60 (m, 2H), 2.62 (s, 3H),3.15-3.35 (m, 2H), 6.50-6.70 (m, 1H), 7.67 (s, 2H).

Examples 247-248

N-Substituted-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamidederivatives (Example 247: N-methyl compound, Example 248: N-ethylcompound) reacted with sulfuryl chloride in the same manner as inExample 246, to give corresponding 4-chloro derivatives.Products/forms/yields/melting points/NMR spectra are described below.

Example 247

N-methyl-4-chloro-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 66.5%/mp: 125-127° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.62 (s,3H), 2.87 (d, J=5.0 Hz, 3H), 6.35-6.70 (m, 1H), 7.67 (s, 2H).

Example 248

N-ethyl-4-chloro-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 48.0%/mp: 85-86° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.17 (t,J=7.2 Hz, 3H), 2.62 (s, 3H), 3.32 (dq, J=6.1 and 7.2 Hz, 2H), 6.40-6.70(m, 1H), 7.67 (m, 2H).

Example 249

Sulfuryl chloride (0.16 g, 1.2 mmol) was added to a solution ofN-isopropyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.40 g, 1.0 mmol) in acetic acid (5 ml), and the mixture was stirred atroom temperature for 4 hours. After completion of the reaction, thereaction mixture was poured into ice water and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant. Thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/20), to give a white solid ofN-isopropyl-4-chloro-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.19 g, yield: 44.1%) [mp: 109-111° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.20 (d, J=7.5 Hz, 6H), 2.61 (s, 3H), 3.85-4.10 (m, 1H), 6.25-6.50 (m,1H), 7.67 (s, 2H).] and a white solid ofN-isopropyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-trichloromethylpyrazole-1-carboxamide(0.04 g, yield: 8.0%) [mp: 105-106° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.22(d, J=6.5 Hz, 6H), 3.85-4.15 (m, 1H), 6.25-6.55 (m, 1H), 7.69 (s, 2H),8.24 (s, 1H)].

Example 250

Sulfuryl chloride (0.09 g, 0.7 mmol) was added to a solution ofN-propyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazole-1-carboxamide(0.24 g, 0.6 mmol) in acetic acid (5 ml), and the mixture was stirred atroom temperature for 4 hours. After completion of the reaction, thereaction mixture was poured into ice water and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant. Thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/20), to give a white solid ofN-propyl-3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-trichloromethylpyrazole-1-carboxamide(0.11 g, yield: 36.7%). mp: 89-91° C.; 1H-NMR (CDCl₃, TMS, ppm): δ 0.90(t, J=7.3 Hz, 3H), 1.56 (tq, J=7.3 and 8.0 Hz, 2H), 3.25 (dt, J=6.3 and8.0 Hz, 2H), 6.50-6.80 (m, 1H), 7.69 (s, 2H), 8.23 (s, 1H).

Example 251

Sulfuryl chloride (0.16 g, 1.2 mmol) was added to a solution ofN-ethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide(0.35 g, 1.0 mmol) in acetic acid (5 ml), and the mixture was stirred atroom temperature for 4 hours. After completion of the reaction, thereaction mixture was poured into ice water and extracted with ethylacetate (10 ml×3). An organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant. Thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-ethyl-4-chloro-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide(0.35 g, yield: 92.1%). mp: 111-112° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.23 (t, J=7.3 Hz, 3H), 2.66 (s, 3H), 3.41 (dq, J=5.8 and 7.3 Hz, 2H),6.85-7.10 (m, 1H), 8.03 (d, J=2.0 Hz, 1H), 8.31 (m, 1H).

Examples 252-260

N-Substituted-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamidederivatives reacted with sulfuryl chloride in the same manner as inExample 251, to give corresponding 4-chloro derivatives.Products/forms/yields/melting points/NMR spectra are described below.

Example 252

N-methyl-4-chloro-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 97.1%/mp: 81-83° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.66 (s,3H), 2.96 (d, J=5.0 Hz, 3H), 6.80-7.15 (m, 1H), 8.04 (d, J=2.1 Hz, 1H),8.32 (m, 1H).

Example 253

N-propyl-4-chloro-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 90.4%/mp: 54-56° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.97 (t,J=7.3 Hz, 3H), 1.62 (tq, J=7.0 and 7.3 Hz, 2H), 2.65 (s, 3H), 3.32 (dt,J=7.0 and 7.3 Hz, 2H), 6.90-7.15 (m, 1H), 8.03 (d, J=2.1 Hz, 1H), 8.31(m, 1H).

Example 254

N-isopropyl-4-chloro-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 89.2%/mp: 57-59° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.25 (d,J=6.5 Hz, 6H), 2.65 (s, 3H), 3.95-4.20 (m, 1H), 6.75-6.95 (m, 1H), 8.04(d, J=2.0 Hz, 1H), 8.32 (m, 1H).

Example 255

N-pentyl-4-chloro-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 80.0%/mp: 76-78° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.90 (t,J=6.9 Hz, 3H), 1.20-1.45 (m, 4H), 1.50-1.70 (m, 2H), 2.65 (s, 3H),3.25-3.45 (m, 2H), 6.85-7.10 (m, 1H), 8.03 (d, J=2.0 Hz, 1H), 8.32 (m,1H).

Example 256

N-hexyl-4-chloro-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 70.6%/mp: 57-59° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.88 (t,J=6.9 Hz, 3H), 1.15-1.45 (m, 6H), 1.45-1.70 (m, 2H), 2.65 (s, 3H),3.20-3.45 (m, 2H), 6.90-7.05 (m, 1H), 8.04 (d, J=2.5 Hz, 1H), 8.32 (m,1H).

Example 257

N-heptyl-4-chloro-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 80.0%/mp: 67-68° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.88 (t,J=7.0 Hz, 3H), 1.10-1.45 (m, 8H), 1.45-1.70 (m, 2H), 2.65 (s, 3H),3.20-3.50 (m, 2H), 6.80-7.10 (m, 1H), 8.03 (d, J=2.0 Hz, 1H), 8.32 (m,1H).

Example 258

N-octyl-4-chloro-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 88.6%/mp: 61-62° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.87 (t,J=6.3 Hz, 3H), 1.15-1.45 (m, 10H), 1.45-1.70 (m, 2H), 2.65 (s, 3H),3.25-3.45 (m, 2H), 6.90-7.10 (m, 1H), 8.03 (d, J=1.8 Hz, 1H), 8.32 (m,1H).

Example 259

N-dodecyl-4-chloro-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 89.9%/mp: 68-70° C./¹H-NMR (CDCl₃, TMS, ppm): δ 0.88 (t,J=6.9 Hz, 3H), 1.15-1.40 (m, 18H), 1.50-1.65 (m, 2H), 2.65 (s, 3H), 3.25(m, 2H), 6.90-7.10 (m, 1H), 8.04 (d, J=1.9 Hz, 1H), 8.25-8.35 (m, 1H).

Example 260

N-cyclohexyl-4-chloro-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 85.7%/mp: 94-96° C./¹H-NMR (CDCl₃, TMS, ppm): δ 1.05-1.50(m, 6H), 1.55-1.90 (m, 2H), 1.90-2.10 (m, 2H), 2.65 (s, 3H), 3.60-3.85(m, 1H), 6.75-7.00 (m, 1H), 8.03 (d, J=1.8 Hz, 1H), 8.32 (m, 1H).

Example 261

N-(2-chloroethyl)-4-chloro-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide/whitesolid/yield: 86.2%/mp: 112-114° C./¹H-NMR (CDCl₃, TMS, ppm): δ 2.65 (s,3H), 3.60-3.80 (m, 4H), 7.30-7.45 (m, 1H), 8.04 (d, J=2.1 Hz, 1H), 8.32(m, 1H).

Example 262

Sulfuryl chloride (0.17 g, 1.2 mmol) was added to a solution ofN-methyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-ethylpyrazole-1-carboxamide(0.35 g, 1.0 mmol) in acetic acid (5 ml), and the mixture was stirred atroom temperature for 5 hours. After completion of the reaction, thereaction mixture was poured into ice water and extracted with ethylacetate (10 ml×3). The organic layer was washed with water, dried overanhydrous magnesium sulfate and filtered to remove a desiccant. Thesolvent was distilled off from the filtrate under reduced pressure. Theresultant crude product was purified with a silica gel column (ethylacetate/hexane=1/10), to give a white solid ofN-methyl-4-chloro-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-ethylpyrazole-1-carboxamide(0.31 g, yield: 80.9%). mp: 88-89° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ 1.30(t, J=7.4 Hz, 3H), 2.96 (d, J=5.0 Hz, 3H), 3.14 (q, J=7.4 Hz, 2H),6.90-7.10 (m, 1H), 8.04 (d, J=2.0 Hz, 1H), 8.32 (m, 1H).

Example 263

N-Bromosuccinimide (0.64 g, 3.6 mmol) was added to a solution ofN-ethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide(1.05 g, 3.0 mmol) in dichloromethane (20 ml), and the mixture wasstirred at room temperature for 6 hours. After completion of thereaction, water was added to the reaction mixture, and the mixture wasextracted with ethyl acetate (10 ml×3). An organic layer was washed withwater, dried over anhydrous magnesium sulfate and filtered to remove adesiccant. The solvent was distilled off from the filtrate under reducedpressure. The resultant crude product was purified with a silica gelcolumn (ethyl acetate/hexane=1/7), to give a white solid ofN-ethyl-4-bromo-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide(0.86 g, yield: 67.0%). mp: 123-125° C.; ¹H-NMR (CDCl₃, TMS, ppm): δ1.23 (t, J=7.3 Hz, 3H), 2.67 (s, 3H), 3.40 (dq, J=5.9 and 7.3 Hz, 2H),6.90-7.10 (m, 1H), 8.04 (d, J=2.0 Hz, 1H), 8.32 (m, 1H).

Example 264

Sodium hydride (60% in oil, 0.03 g, 0.7 mmol) was added to a solution ofethyl3-[{3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazol-1-yl}carbonylamino]propionate(0.30 g, 0.7 mmol) in DMF (5 ml) at 0° C., and the mixture was stirredat an ambient temperature for 30 minutes. Then, methyl iodide (0.10 g,0.7 mmol) was added, and the mixture was allowed to have roomtemperature gradually and stirred overnight. After completion of thereaction, the reaction mixture was poured into water (10 ml) andextracted with ethyl acetate (10 ml×2). An organic layer was washed withwater (10 ml×3), dried over anhydrous magnesium sulfate and filtered toremove a desiccant. The solvent was distilled off from the filtrateunder reduced pressure. The resultant crude product was purified with asilica gel column (ethyl acetate/hexane=1/15), to give a colorlessviscous substance of ethyl3-[{3-(2,6-dichloro-4-trifluoromethylphenyloxy)-5-methylpyrazol-1-yl}carbonyl]methylamino]propionate(0.23 g, yield: 74.4%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.28 (t, J=7.1 Hz,3H), 2.22-2.40 (m, 2H), 2.45 (s, 3H), 2.96 (s, 3H), 3.57 (m, 2H), 4.12(q, J=7.1 Hz, 2H), 5.83 (s, 1H), 7.63 (s, 2H).

Example 265

Chloromethyl methyl ether (0.16 g, 2.0 mmol) was added to a solution ofsodium hydride (60% in oil, 0.09 g, 2.2 mmol) andN-methyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide(0.67 g, 2.0 mmol) in DMF (10 ml) at 0° C., and while the mixture wasallowed to have room temperature gradually, the mixture was stirredovernight. After completion of the reaction, water was added to thereaction mixture, and the mixture was extracted with ethyl acetate (10ml×3). An organic layer was washed with water, dried over anhydrousmagnesium sulfate and filtered to remove a desiccant. The solvent wasdistilled off from the filtrate under reduced pressure. The resultantcrude product was purified with a silica gel column (ethylacetate/hexane=1/5), to give a colorless viscous substance ofN-methyl-N-methoxymethyl-3-(3-chloro-5-trifluoromethylpyridin-2-yloxy)-5-methylpyrazole-1-carboxamide(0.18 g, yield: 23.8%). ¹H-NMR (CDCl₃, TMS, ppm): δ 1.87 (s, 3H), 3.52(s, 3H), 3.53 (s, 3H), 5.18 (s, 2H), 5.46 (s, 1H), 7.80-7.95 (m, 1H),8.50-8.65 (m, 1H).

The following Tables 1 to 4 show compounds of the present invention thatcan be synthesized by those processes shown in the above ProductionExamples, Referential Examples and Examples. The present invention shallnot be limited to these compounds. Abbreviations in Tables have thefollowing meanings. Me: methyl; Et: ethyl, Pr: propyl; i-Pr: isopropyl;c-Pr: cyclopropyl, Bu: butyl; i-Bu: isobutyl; s-Bu: secondary butyl;t-Bu: tertiary butyl; Pent: pentyl; c-Pent: cyclopentyl; Hex: hexyl;c-Hex: cyclohexyl; Hep: heptyl; Oct: octyl; Dod: dodecyl;

*1): tetrahydrofurfuryl;

*2): (1,3-dioxa-2-cyclopentyl)methyl;

*3): (1,3-dioxa-2-cyclohexyl)methyl;

*4): furfuryl;

*5): 2-morpholinoethyl;

*6): 2-picolyl;

*7): 2-thienylmethyl;

*8): (4-chloro-5-cyclopentyloxy-2-fluoro)phenyl;

TABLE 1 3-(Substituted phenyloxy)pyrazole derivatives

Compound No. Example No. R¹ R² Xn 1-1 H H 2,6-Cl₂-4-CF₃ 1-2 H H2-Cl-6-F-4-CF₃ 1-3 47 Me H H 1-4 3 Me H 3-Me-4-NO₂ 1-5 4 Me H3-MeO-4-NO₂ 1-6 40 Me H 3-EtO-4-NO₂ 1-7 41 Me H 5-EtO-2-NO₂ 1-8 48 Me H3-Cl 1-9 Me Cl 3-Cl 1-10 Me H 2-Cl-4-CF₃ 1-11 Me Cl 2-Cl-4-CF₃ 1-12 51Me H 4-Cl-2-CF₃ 1-13 Me Cl 4-Cl-2-CF₃ 1-14 50 Me H 4-Cl-3-CF₃ 1-15 Me Cl4-Cl-3-CF₃ 1-16 Me H 4-F-3-CF₃ 1-17 18 Me H 2,6-Cl₂-4-CF₃ 1-18 52 Me Cl2, 6-Cl₂-4-CF₃ 1-19 29 Me H 2-Cl-6-F-4-CF₃ 1-20 Me Cl 2-Cl-6-F-4-CF₃1-21 31 Me H 2-Cl-6-NO₂-4-CF₃ 1-22 44 Me H 3-Cl-4-NH₂ 1-23 14 Me H3-Cl-4-NO₂ 1-24 Me Cl 3-Cl-4-NO₂ 1-25 14 Me H 5-Cl-2-NO₂ 1-26 15 Me H3-F-4-NO₂ 1-27 Me Cl 3-F-4-NO₂ 1-28 15 Me H 5-F-2-NO₂ 1-29 2 Me H4-F-2-NO₂ 1-30 17 Me H 4-CN-2-CF₃ 1-31 49 Me H 2-CF₃ 1-32 46 Me H 3-CF₃1-33 Me Cl 3-CF₃ 1-34 Me H 2,4-(CF₃)₂ 1-35 Me Cl 2,4-(CF₃)₂ 1-36 43 Me H4-NH₂ 1-37 42 Me H 4-NH₂-2-CF₃ 1-38 45 Me H 4-NH₂-3-CF₃ 1-39 Me H2-NH₂-4-CF₃ 1-40 10 Me H 4-NO₂-2-CF₃ 1-41 Me Cl 4-NO₂-2-CF₃ 1-42 16 Me H4-NO₂-3-CF₃ 1-43 Me Cl 4-NO₂-3-CF₃ 1-44 5 Me H 2-NO₂-4-CF₃ 1-45 Me Cl2-NO₂-4-CF₃ 1-46 30 Me H 2,4-(NO₂)₂-6-CF₃ 1-47 1 Me H 4-NO₂ 1-48 26 MeMe 2,6-Cl₂-4-CF₃ 1-49 Me Me 2-Cl-6-F-4-CF₃ 1-50 12 Me Me 4-NO₂-2-CF₃1-51 8 Me Me 2-NO₂-4-CF₃ 1-52 27 Me Et 2,6-Cl₂-4-CF₃ 1-53 Me Et2-Cl-6-F-4-CF₃ 1-54 13 Me Et 4-NO₂-2-CF₃ 1-55 9 Me Et 2-NO₂-4-CF₃ 1-5619 Et H 2,6-Cl₂-4-CF₃ 1-57 Et Cl 2,6-Cl₂-4-CF₃ 1-58 Et H 2-Cl-6-F-4-CF₃1-59 Et Cl 2-Cl-6-F-4-CF₃ 1-60 11 Et H 4-NO₂-2-CF₃ 1-61 Et Cl4-NO₂-2-CF₃ 1-62 7 Et H 2-NO₂-4-CF₃ 1-63 Et Cl 2-NO₂-4-CF₃ 1-64 Pr H2,6-Cl₂-4-CF₃ 1-65 Pr H 2-Cl-6-F-4-CF₃ 1-66 20 i-Pr H 2,6-Cl₂-4-CF₃ 1-67i-Pr H 2-Cl-6-F-4-CF₃ 1-68 22 c-Pr H 2,6-Cl₂-4-CF₃ 1-69 c-Pr H2-Cl-6-F-4-CF₃ 1-70 21 t-Bu H 2,6-Cl₂-4-CF₃ 1-71 t-Bu H 2-Cl-6-F-4-CF₃1-72 23 MeOCH₂ H 2,6-Cl₂-4-CF₃ 1-73 MeOCH₂ H 2-Cl-6-F-4-CF₃ 1-74 25MeO₂CCH₂ H 2,6-Cl₂-4-CF₃ 1-75 MeO₂CCH₂ H 2-Cl-6-F-4-CF₃ 1-76 CF₃ H2,6-Cl₂-4-CF₃ 1-77 6 CF₃ H 2-NO₂-4-CF₃ 1-78 CF₃ H 2-Cl-6-F-4-CF₃ 1-79 24MeO₂C H 2,6-Cl₂-4-CF₃ 1-80 MeO₂C H 2-Cl-6-F-4-CF₃ 1-81 EtO₂C H2,6-Cl₂-4-CF₃ 1-82 EtO₂C H 2-Cl-6-F-4-CF₃ 1-83 28 4-Cl-C₆H₄ H2,6-Cl₂-4-CF₃ 1-84 4-Cl-C₆H₄ H 2-Cl-6-F-4-CF₃

TABLE 2 3-(Substituted pyridyloxy)pyrazole derivatives

Compound No. Example No. R¹ R² Xn 2-1 H H 3-Cl-5-CF₃ 2-2 34 Me H4-Me-5-NO₂ 2-3 33 Me H 6-MeO-3-NO₂ 2-4 32 Me H 3,5-Cl₂ 2-5 35 Me H3-Cl-5-CF₃ 2-6 Me Cl 3-Cl-5-CF₃ 2-7 Me H 5-CF₃ 2-8 Me H 3,5-(NO₂)₂ 2-938 Me Me 3-Cl-5-CF₃ 2-10 39 Me Et 3-Cl-5-CF₃ 2-11 37 Et H 3-Cl-5-CF₃2-12 Et Cl 3-Cl-5-CF₃ 2-13 Pr H 3-Cl-5-CF₃ 2-14 i-Pr H 3-Cl-5-CF₃ 2-15c-Pr H 3-Cl-5-CF₃ 2-16 t-Bu H 3-Cl-5-CF₃ 2-17 MeOCH₂ H 3-Cl-5-CF₃ 2-18MeO₂CCH₂ H 3-Cl-5-CF₃ 2-19 36 CF₃ H 3-Cl-5-CF₃ 2-20 MeO₂C H 3-Cl-5-CF₃2-21 4-Cl-C₆H₄ H 3-Cl-5-CF₃

TABLE 3 Synthesis of 3-(substituted Phenyloxy)pyrazole derivatives

Compound Example No. No. R¹ R² R³ R⁴ Xn Y 3-1 H H H H 2,6-Cl₂-4-CF₃ O3-2 H H H H 2-Cl-6-F-4-CF₃ O 3-3 223 Me H H H 2,6-Cl₂-4-CF₃ O 3-4 Me H HH 2,6-Cl₂-4-CF₃ S 3-5 224 Me H H H 2-Cl-6-F-4-CF₃ O 3-6 Me H H H2-Cl-6-F-4-CF₃ S 3-7 Me H H H 2-Cl-4-NO₂-6-CF₃ O 3-8 226 Me H H H 3-CF₃O 3-9 Me H H H 4-NO₂-2-CF₃ O 3-10 Me H H H 4-NO₂-3-CF₃ O 3-11 Me H H H2-NO₂-4-CF₃ O 3-12 118 Me H Me H 2-Cl-6-F-4-CF₃ O 3-13 Me H Me H2-Cl-6-F-4-CF₃ S 3-14 105 Me H Me H 2,6-Cl₂-4-CF₃ O 3-15 179 Me H Me H2,6-Cl₂-4-CF₃ S 3-16 Me H Me Me 2,6-Cl₂-4-CF₃ O 3-17 Me H Me Me2,6-Cl₂-4-CF₃ S 3-18 Me H Me Et 2,6-Cl₂-4-CF₃ O 3-19 Me H Me Et2,6-Cl₂-4-CF₃ S 3-20 Me H Me MeOCH₂ 2,6-Cl₂-4-CF₃ O 3-21 Me H Me MeOCH₂2,6-Cl₂-4-CF₃ S 3-22 Me H Me EtOCH₂ 2,6-Cl₂-4-CF₃ O 3-23 Me H Me EtOCH₂2,6-Cl₂-4-CF₃ S 3-24 127 Me H Me H 2-Cl-4-NO₂-6-CF₃ O 3-25 Me H Me H2-Cl-4-NO₂-6-CF₃ S 3-26 Me H Me H 4-NH₂-2-CF₃ O 3-27 Me H Me H4-NH₂-3-CF₃ O 3-28 242 Me H Me H 2-NH₂-4-CF₃ O 3-29 92 Me H Me H4-NO₂-2-CF₃ O 3-30 Me H Me H 4-NO₂-2-CF₃ S 3-31 103 Me H Me H4-NO₂-3-CF₃ O 3-32 Me H Me H 4-NO₂-3-CF₃ S 3-33 87 Me H Me H 2-NO₂-4-CF₃O 3-34 Me H Me Me 2-NO₂-4-CF₃ O 3-35 Me H Me H 2-NO₂-4-CF₃ S 3-36 Me HMe H 2,4-(NO₂)₂-6-CF₃ O 3-37 Me H Me H 2,4-(NO₂)₂-6-CF₃ S 3-38 Me H Me H4-NO₂ O 3-39 Me H Me H 4-NO₂ S 3-40 53 Me H Et H H O 3-41 97 Me H Et H3-Me-4-NO₂ O 3-42 98 Me H Et H 3-EtO-4-NO₂ O 3-43 99 Me H Et H5-EtO-2-NO₂ O 3-44 106 Me H Et H 2,6-Cl₂-4-CF₃ O 3-45 180 Me H Et H2,6-Cl₂-4-CF₃ S 3-46 119 Me H Et H 2-Cl-6-F-4-CF₃ O 3-47 186 Me H Et H2-Cl-6-F-4-CF₃ S 3-48 Me H Et H 2-Cl-4-CF₃ O 3-49 Me H Et H 2-Cl-4-CF₃ S3-50 84 Me H Et H 4-Cl-2-CF₃ O 3-51 101 Me H Et H 4-Cl-3-CF₃ O 3-52 124Me H Et H 2,6-F₂-4-CF₃ O 3-53 Me H Et Me 2,6-Cl₂-4-CF₃ O 3-54 Me H Et Et2,6-Cl₂-4-CF₃ O 3-55 Me H Et MeOCH₂ 2,6-Cl₂-4-CF3 O 3-56 Me H Et EtOCH₂2,6-C12-4-CF3 O 3-57 126 Me H Et H 2-Cl-4-NO₂-6-CF₃ O 3-58 Me H Et H2-Cl-4-NO₂-6-CF₃ S 3-59 85 Me H Et H 4-F-2-NO₂ O 3-60 57 Me H Et H 3-CF₃O 3-61 95 Me H Et H 4-CN-2-CF₃ O 3-62 Me H Et H 4-NH₂-2-CF₃ O 3-63 100Me H Et H 4-NH₂-3-CF₃ O 3-64 Me H Et H 2-NH₂-4-CF₃ O 3-65 93 Me H Et H4-NO₂-2-CF₃ O 3-66 104 Me H Et H 4-NO₂-3-CF₃ O 3-67 88 Me H Et H2-NO₂-4-CF₃ O 3-68 125 Me H Et H 2,4-(NO₂)₂-6-CF₃ O 3-69 54 Me H Et H4-NO₂ O 3-70 Me H Pr H 2-Cl-4-CF₃ O 3-71 Me H Pr H 4-Cl-3-CF₃ O 3-72 121Me H Pr H 2-Cl-6-F-4-CF₃ O 3-73 Me H Pr H 2-Cl-6-F-4-CF₃ S 3-74 107 Me HPr H 2,6-Cl₂-4-CF₃ O 3-75 181 Me H Pr H 2,6-Cl₂-4-CF₃ S 3-76 128 Me H PrH 2,Cl-4-NO₂-6-CF₃ O 3-77 Me H Pr H 2-Cl-4-NO₂-6-CF₃ S 3-78 91 Me H Pr H4-NO₂-2-CF₃ O 3-79 Me H Pr H 4-NO₂-2-CF₃ S 3-80 102 Me H Pr H4-NO₂-3-CF₃ O 3-81 Me H Pr H 4-NO₂-3-CF₃ S 3-82 89 Me H Pr H 2-NO₂-4-CF₃O 3-83 Me H Pr H 2-NO₂-4-CF₃ S 3-84 56 Me H i-Pr H 3-CF₃ O 3-85 Me Hi-Pr H 2-Cl-4-CF₃ O 3-86 Me H i-Pr H 4-Cl-3-CF₃ O 3-87 120 Me H i-Pr H2-Cl-6-F-4-CF₃ O 3-88 Me H i-Pr H 2-Cl-6-F-4-CF₃ S 3-89 108 Me H i-Pr H2,6-Cl₂-4-CF₃ 0 3-90 182 Me H i-Pr H 2,6-Cl₂-4-CF₃ S 3-91 94 Me H i-Pr H2-NO₂-2-CF₃ O 3-92 Me H i-Pr H 4-NO₂-2-CF₃ S 3-93 90 Me H i-Pr H2-NO₂-4-CF₃ O 3-94 Me H i-Pr H 2-NO₂-4-CF₃ S 3-95 132 Me H i-Pr i-Pr2-NO₂-4-CF₃ O 3-96 Me H Bu H 2-Cl-6-F-4-CF₃ O 3-97 Me H Bu H2-Cl-6-F-4-CF₃ S 3-98 Me H Eu H 2,6-Cl₂-4-CF₃ O 3-99 183 Me H Bu H2,6-Cl₂4-CF₃ S 3-100 Me H i-Bu H 2-Cl-6-F-4-CF₃ O 3-101 Me H i-Bu H2-Cl-6-F-4-CF3 S 3-102 Me H i-Eu H 2,6-Cl₂-4-CF₃ O 3-103 Me H s-Bu H2-Cl-6-F-4-CF₃ 0 3-104 Me H s-Bu H 2-Cl-6-F-4-CF₃ S 3-105 202 Me H s-BuH 2,6-Cl₂-4-CF₃ O 3-106 58 Me H t-Bu H 3-CF₃ O 3-107 109 Me H t-Bu H2,6-Cl₂-4-CF₃ O 3-108 Me H t-Bu H 2-Cl-6-F-4-CF₃ O 3-109 86 Me H t-Bu H2-NO₂-4-CF₃ O 3-110 Me H Pent H 2,6-Cl₂-4-CF₃ O 3-111 Me H 3-Pent H2-Cl-6-F-4-CF₃ O 3-112 203 Me H 3-Pent H 2,6-Cl₂-4-CF₃ O 3-113 59 Me HHex H 3-CF₃ O 3-114 110 Me H Hex H 2,6-Cl₂-4-CF₃ O 3-115 Me H Hex H2-Cl-6-F-4-CF₃ O 3-116 Me H Hep H 2,6-Cl₂-4-CF₃ O 3-117 Me H Hep H2-Cl-6-F-4-CF₃ O 3-118 111 Me H Oct H 2,6-Cl₂-4-CF₃ O 3-119 Me H Oct H2-Cl-6-F-4-CF₃ O 3-120 Me H Dod H 2,6-Cl₂-4-CF₃ O 3-121 Me H Dod H2-Cl-6-F-4-CF₃ O 3-122 201 Me H c-Pr H 2,6-Cl₂-4-CF₃ O 3-123 Me H c-Pr H2,6-Cl₂-4-CF₃ S 3-124 Me H c-Pr H 2-Cl-6-F-4-CF₃ O 3-125 204 Me H c-PentH 2,6-Cl₂-4-CF₃ O 3-126 Me H c-Pent H 2-Cl-6-F-4-CF₃ O 3-127 60 Me Hc-Hex H 3-CF₃ O 3-128 Me H c-Hex H 2,6-Cl₂-4-CF₃ O 3-129 Me H c-Hex H2-Cl-6-F-4-CF₃ O 3-130 112, 234 Me H H₂C═CHCH₂ H 2,6-Cl₂-4-CF₃ O 3-131Me H H₂C═CHCH₂ H 2,6-Cl₂-4-CF₃ S 3-132 122 Me H H₂C═CHCH₂ H2-Cl-6-F-4-CF₃ O 3-133 Me H H₂C═CHCH₂ H 2-Cl-6-F-4-CF₃ S 3-134 61 Me HH₂C═CHCH₂ H 3-CF₃ O 3-135 Me H H₂C═CHCH₂ H 3-CF₃ S 3-136 205 Me HHC≡CCH₂ H 2,6-Cl₂-4-CF₃ O 3-137 Me H HC≡CCH₂ H 2-Cl-6-F-4-CF₃ O 3-138229 Me H HCOCH₂ H 2,6-Cl₂-4-CF₃ O 3-139 Me H HCOCH₂ H 2-Cl-6-F-4-CF₃ O3-140 211 Me H CF₃CH₂ H 2,6-Cl₂-4-CF₃ O 3-141 Me H CF₃CH₂ H2-Cl-6-F-4-CF₃ O 3-142 62 Me H 2-ClC₂H₄ H 3-CF₃ O 3-143 113 Me H2-ClC₂H₄ H 2,6-Cl₂-4-CF₃ O 3-144 Me H 2-ClC₂H₄ H 2,6-Cl₂-4-CF₃ S 3-145Me H 2-ClC₂H₄ H 2-Cl-6-F-4-CF₃ O 3-146 114 Me H 2-BrC₂H₄ H 2,6-Cl₂-4-CF₃O 3-147 Me H 2-BrC₂H₄ H 2,6-Cl₂-4-CF₃ S 3-148 123 Me H 2-BrC₂H₄ H2-Cl-6-F-4-CF₃ O 3-149 Me H 2-FC₂H₄ H 2,6-Cl₂-4-CF₃ O 3-150 Me H 2-FC₂H₄H 2-Cl-6-F-4-CF₃ O 3-151 210 Me H 2-HOC₂H₄ H 2,6-Cl₂-4-CF₃ O 3-152 Me H2-HOC₂H₄ H 2-Cl-6-F-4-CF₃ O 3-153 Me H MeO H 2,6-Cl₂-4-CF₃ O 3-154 Me HMeO H 2,6-Cl₂-4-CF₃ S 3-155 Me H MeO H 2-Cl-6-F-4-CF₃ O 3-156 Me H MeO H2-Cl-6-F-4-CF₃ S 3-157 198 Me H EtO H 3-CF₃ O 3-158 206 Me H EtO H2,6-Cl₂-4-CF₃ O 3-159 Me H EtO H 2,6-Cl₂-4-CF₃ S 3-160 Me H EtO H2-Cl-6-F-4-CF₃ O 3-161 Me H EtO H 2-Cl-6-F-4-CF₃ S 3-162 207 Me H t-BuOH 2,6-Cl₂-4-CF₃ O 3-163 Me H t-BuO H 2-Cl-6-F-4-CF₃ O 3-164 208 Me HH₂C═CHCH₂O H 2,6-Cl₂-4-CF₃ O 3-165 Me H H₂C═CHCH₂O H 2-Cl-6-F-4-CF₃ O3-166 209 Me H C₆H₅CH₂O H 2,6-Cl₂-4-CF₃ O 3-167 Me H H₂C═CHCH₂O H2-Cl-6-F-4-CF₃ O 3-168 Me H MeOCH₂ H 2,6-Cl₂-4-CF₃ O 3-169 178 Me HMeOCH₂ H 2,6-Cl₂-4-CF₃ S 3-170 Me H MeOCH₂ H 2-Cl-6-F-4-CF₃ O 3-171 Me HMeOCH₂ H 2-Cl-6-F-4-CF₃ S 3-172 177 Me H MeOCH₂ H 4-CN-2-CF₃ S 3-173 MeH MeOCH₂ H 4-NO₂-2-CF₃ O 3-174 Me H MeOCH₂ H 2-NO₂-4-CF₃ O 3-175 Me HMeOCH₂CH₂ H 2,6-Cl₂-4-CF₃ O 3-176 184 Me H MeOCH₂CH₂ H 2,6-Cl₂-4-CF₃ S3-177 Me H MeOCH₂CH₂ H 2-Cl-6-F-4-CF₃ O 3-178 Me H MeOCH₂CH₂ H2-Cl-6-F-4-CF₃ S 3-179 232 Me H (MeO)₂CHCH₂ H 2,6-Cl₂-4-CF₃ O 3-180 Me H(MeO)₂CHCH₂ H 2-Cl-6-F-4-CF₃ O 3-181 199 Me H *1) H 3-CF₃ O 3-182 200 MeH *1) H 4-Cl-2-CF₃ O 3-183 212 Me H *1) H 2,6-Cl₂-4-CF₃ O 3-184 185 Me H*1) H 2,6-Cl₂-4-CF₃ S 3-185 217 Me H *1) H 2-Cl-6-F-4-CF₃ O 3-186 230 MeH *2) H 2,6-Cl₂-4-CF₃ O 3-187 Me H *2) H 2,Cl-6-F-4-CF₃ O 3-188 231 Me H*3) H 2,6-Cl₂-4-CF₃ O 3-189 Me H *3) H 2,Cl-6-F-4-CF₃ O 3-190 213 Me H*4) H 2,6-Cl₂-4-CF₃ O 3-191 Me H *4) H 2-Cl-6-F-4-CF₃ O 3-192 214 Me H*5) H 2,6-Cl₂-4-CF₃ O 3-193 Me H *5) H 2-Cl-6-F-4-CF₃ O 3-194 215 Me H*6) H 2,6-Cl₂-4-CF₃ O 3-195 Me H *6) H 2-Cl-6-F-4-CF₃ O 3-196 216 Me H*7) H 2,6-Cl₂-4-CF₃ O 3-197 Me H *7) H 2-Cl-6-F-4-CF₃ O 3-198 116 Me HEtO₂CCH₂ H 2,6-Cl₂-4-CF₃ O 3-199 Me H EtO₂CCH₂ H 2-Cl-6-F-4-CF₃ O 3-20063 Me H EtO₂CCH₂ H 3-CF₃ O 3-201 117 Me H EtO₂C(CH₂)₂ H 2,6-Cl₂-4-CF₃ O3-202 Me H EtO₂C(CH₂)₂ H 2-Cl-6-F-4-CF₃ O 3-203 264 Me H EtO₂C(CH₂)₂ Me2,6-Cl₂-4-CF₃ O 3-204 83 Me H C₆H₅ H 3-Cl O 3-205 55 Me H C₆H₅ H 2-CF₃ O3-206 64 Me H C₆H₅ H 3-CF₃ O 3-207 67 Me H 3-Me-C₆H₄ H 3-CF₃ O 3-208 76Me H 2-Cl-4-Me-C₆H₃ H 3-CF₃ O 3-209 78 Me H 2-Cl-6-Me-C₆H₃ H 3-CF₃ O3-210 77 Me H 2-Me-4-NO₂-C₆H₃ H 3-CF₃ O 3-211 65 Me H 2-Cl-C₆H₄ H 3-CF₃O 3-212 66 Me H 3-Cl-C₆H₄ H 3-CF₃ O 3-213 Me H 3-Cl-C₆H₄ H 2,6-Cl₂-4-CF₃O 3-214 69 Me H 4-Cl-C₆H₄ H 3-CF₃ O 3-215 Me H 4-Cl-C₆H₄ H 2,6-Cl₂-4-CF₃O 3-216 80 Me H *8) H 3-CF₃ O 3-217 70 Me H 4-F-C₆H₄ H 3-CF₃ O 3-218 MeH 4-F-C₆H₄ H 2,6-Cl₂-4-CF₃ O 3-219 72 Me H 2,4-Cl₂-C₆H₃ H 3-CF₃ O 3-220Me H 2,4-Cl₂-C₆H₃ H 2,6-Cl₂-4-CF₃ O 3-221 Me H 2,4-Cl₂-C₆H₃ H2-Cl-6-F-4-CF₃ O 3-222 75 Me H 2,6-Cl₂-C₆H₃ H 3-CF₃ O 3-223 Me H2,6-Cl₂-C₆H₃ H 2,6-Cl₂-4-CF₃ O 3-224 Me H 2,6-Cl₂-C₆H₃ H 2,Cl-6-F-4-CF₃O 3-225 Me H 3,4-Cl₂-C₆H₃ H 3-CF₃ O 3-226 Me H 3,4-Cl₂-C₆H₃ H2,6-Cl₂-4-CF₃ O 3-227 Me H 3,4-Cl₂-C₆H₃ H 2,Cl-6-F-4-CF₃ O 3-228 74 Me H3,4-Cl₂-C₆H₃ H 3-CF₃ O 3-229 73 Me H 2,4-F₂-C₆H₃ H 3-CF₃ O 3-230 79 Me H2,3,4-Cl₃-C₆H₂ H 3-CF₃ O 3-231 Me H 3-CF₃-C₆H₄ H 2,6-Cl₂-4-CF₃ O 3-232Me H 3-CF₃-C₆H₃ H 2-Cl-6-F-4-CF₃ O 3-233 71 Me H 4-CF₃-C₆H₄ H 3-CF₃ O3-234 Me H 4-CF₃-C₆H₄ H 2,6-Cl₂-4-CF₃ O 3-235 Me H 4-CF₃-C₆H₃ H2-Cl-6-F-4-CF₃ O 3-236 70 Me H 3-NO₂-C₆H₄ H 3-CF₃ O 3-237 Me H3-NO₂-C₆H₄ H 2,6-Cl₂-4-CF₃ O 3-238 Me H 3-NO₂-C₆H₄ H 2-Cl-6-F-4-CF₃ O3-239 Me H 4-NO₂-C₆H₄ H 2,6-Cl₂-4-CF₃ O 3-240 81 Me H C₆H₅CH₂ H 3-CF₃ O3-241 115 Me H C₆H₅CH₂ H 2,6-Cl₂-4-CF₃ O 3-242 Me H C₆H₅CH₂ H2-Cl-6-F-4-CF₃ O 3-243 Me H 3-Cl-C₆H₄CH₂ H 2,6-Cl₂-4-CF₃ O 3-244 Me H3-Cl-C₆H₄CH₂ H 2-Cl-6-F-4-CF₃ O 3-245 Me H 4-Cl-C₆H₄CH₂ H 2,6-Cl₂-4-CF₃O 3-246 Me H 4-Cl-C₆H₄CH₂ H 2-Cl-6-F-4-CF₃ O 3-247 82 Me H C₆H₅C(CH₃)H H3-CF₃ O 3-248 Me Cl H H 2,6-Cl₂-4-CF₃ O 3-249 247 Me Cl Me H2,6-Cl₂-4-CF₃ O 3-250 Me Cl Me H 2-Cl-6-F-4-CF₃ O 3-251 245 Me Cl Me H4-NO₂-2-CF₃ O 3-252 244 Me Cl Me H 2-NO₂-4-CF₃ O 3-253 248 Me Cl Et H2,6-Cl₂-4-CF₃ O 3-254 Me Cl Et H 2,-6-Cl₂-4-CF₃ S 3-255 Me Cl Et H2-Cl-6-F-4-CF₃ O 3-256 Me Cl Et H 2-Cl-6-F-4-CF₃ S 3-257 Me Cl Pr H2,6-Cl₂-4-CF₃ O 3-258 Me Cl Pr H 2-Cl-6-F-4-CF₃ O 3-259 249 Me Cl i-Pr H2,6-Cl₂-4-CF₃ O 3-260 Me Cl i-Pr H 2-Cl-6-F-4-CF₃ O 3-261 243 Me Cl i-PrH 2-NO₂-4-CF₃ O 3-262 Me Cl Bu H 2,6-Cl₂-4-CF₃ O 3-263 Me Cl Bu H2-Cl-6-F-4-CF₃ O 3-264 Me Cl s-Bu H 2,6-Cl₂-4-CF₃ O 3-265 Me Cl s-Bu H2-Cl-6-F-4-CF₃ O 3-266 246 Me Cl Hex H 2,6-Cl₂-4-CF₃ O 3-267 Me Cl Hex H2-Cl-6-F-4-CF₃ O 3-268 Me Cl c-Pr H 2,6-Cl₂-4-CF₃ O 3-269 Me Cl c-Pr H2,Cl-6-F-4-CF₃ O 3-270 160 Me Cl ClC₂H₄ H 2,6-Cl₂-4-CF₃ O 3-271 Me ClClC₂H₄ H 2-Cl-6-F-4-CF₃ O 3-272 Me Cl MeOCH₂ H 2,6-Cl₂-4-CF₃ O 3-273 MeCl MeOCH₂ H 2-Cl-6-F-4-CF₃ O 3-274 Me Cl MeOCH₂CH₂ H 2,6-Cl₂-4-CF₃ O3-275 Me Cl MeOCH₂CH₂ H 2-Cl-6-F-4-CF₃ O 3-276 Me Br H H 2,6-Cl₂-4-CF₃ O3-277 Me Br H H 2,6-Cl₂-4-CF₃ S 3-278 Me Br H H 2-Cl-6-F-4-CF₃ O 3-279Me Br H H 2-Cl-6-F-4-CF₃ S 3-280 Me Br Me H 2,6-Cl₂-4-CF₃ O 3-281 Me BrMe H 2-Cl-6-F-4-CF₃ O 3-282 Me Br Et H 2,6-Cl₂-4-CF₃ O 3-283 Me Br Et H2-Cl-6-F-4-CF₃ O 3-284 Me Br Pr H 2,6-Cl₂-4-CF₃ O 3-285 Me Br Pr H2-Cl-6-F-4-CF₃ O 3-286 Me Me H H 2,6-Cl₂-4-CF₃ O 3-287 Me Me H H2,6-Cl₂-4-CF₃ S 3-288 Me Me H H 2-Cl-6-F-4-CF₃ O 3-289 Me Me H H2-Cl-6-F-4-CF₃ S 3-290 Me Me Me H 2,6-Cl₂-4-CF₃ O 3-291 Me Me Me H2,6-Cl₂4-CF₃ S 3-292 Me Me Me H 2-Cl-6-F-4-CF₃ O 3-293 Me Me Me H2-Cl-6-F-4-CF₃ S 3-294 152 Me Me Me H 4-NO₂-2-CF₃ O 3-295 151 Me Me Me H2-NO₂-4-CF₃ O 3-296 Me Me Et H 2,6-Cl₂-4-CF₃ O 3-297 Me Me Et H2,6-Cl₂-4-CF₃ S 3-298 Me Me Et H 2-Cl-6-F-4-CF₃ O 3-299 Me Me Et H2-Cl-6-F-4-CF₃ S 3-300 Me Me Et H 4-NO₂-2-CF₃ O 3-301 Me Me Et H2-NO₂-4-CF₃ O 3-302 Me Me Pr H 2,6-Cl₂-4-CF₃ O 3-303 Me Me Pr H2,6-Cl₂-4-CF₃ S 3-304 Me Me Pr H 2-Cl-6-F-4-CF₃ O 3-305 Me Me Pr H2-Cl-6-F-4-CF₃ S 3-306 Me Me i-Pr H 2,6-Cl₂-4-CF₃ O 3-307 Me Me i-Pr H2,6-Cl₂-4-CF₃ S 3-308 Me Me i-Pr H 2-Cl-6-F-4-CF₃ O 3-309 Me Me i-Pr H2-Cl-6-F-4-CF₃ S 3-310 Me Et H H 2,6-Cl₂-4-CF₃ O 3-311 Me Et H H2-Cl-6-F-4-CF₃ O 3-312 Me Et Me H 2,6-Cl₂-4-CF₃ O 3-313 Me Et Me H2,6-Cl₂-4-CF₃ S 3-314 Me Et Me H 2-Cl-6-F-4-CF₃ O 3-315 Me Et Me H2-Cl-6-F-4-CF₃ S 3-316 157 Me Et Me H 4-NO₂-2-CF₃ O 3-317 156 Me Et Me H2-NO₂-4-CF₃ O 3-318 169 Me Et Et H 2,6-Cl₂-4-CF₃ O 3-319 227 Me H—CH₂CH₂CH₂CH₂— 2,6-Cl₂4-CF₃ O 3-320 Me H —CH₂CH₂CH₂CH₂— 2-Cl-6-F-4-CF₃ O3-321 228 Me H —CH₂C (CH₂) OC (CH₂) CH₂— 2,6-Cl₂-4-CF₃ O 3-322 Me H—CH₂C (CH₂) OC (CH₂) CH₂— 2-Cl-6-F-4-CF₃ O 3-323 Et H H H 2,6-Cl₂-4-CF₃O 3-324 Et H H H 2-Cl-6-F-4-CF₃ O 3-325 Et H Me H 2,6-Cl₂-4-CF₃ O 3-323Et H Me H 2-Cl-6-F-4-CF₃ O 3-327 162 Et H Me H 4-NO₂-2-CF₃ O 3-328 Et HMe H 2-Cl-6-F-4-CF₃ O 3-329 161 Et H Me H 2-NO₂-4-CF₃ O 3-330 163 Et HEt H 2,6-Cl₂-4-CF₃ O 3-331 Et H Et H 2,6-Cl₂-4-CF₃ S 3-332 Et H Et H2-Cl-6-F-4-CF₃ O 3-333 Et H Et H 2-Cl-6-F-4-CF₃ S 3-334 Et H Pr H2,6-Cl₂-4-CF₃ O 3-335 Et H Pr H 2-Cl-6-F-4-CF₃ O 3-336 Pr H H H2,6-Cl₂-4-CF₃ O 3-337 Pr H H H 2-Cl-6-F-4-CF₃ O 3-338 Pr H Me H2,6-Cl₂-4-CF₃ O 3-339 Pr H Me H 2-Cl-6-F-4-CF₃ O 3-340 Pr H Et H2,6-Cl₂-4-CF₃ O 3-341 i-Pr H H H 2,6-Cl₂-4-CF₃ O 3-342 i-Pr H H H2-Cl-6-F-4-CF₃ O 3-343 i-Pr H Me H 2,6-Cl₂-4-CF₃ O 3-344 i-Pr H Me H2-Cl-6-F-4-CF₃ O 3-345 167 i-Pr H Et H 2,6-Cl₂-4-CF₃ 0 3-346 i-Pr H Et H2-Cl-6-F-4-CF₃ O 3-347 s-Bu H Et H 2,6-Cl₂-4-CF₃ O 3-348 s-Bu H Et H2-Cl-6-F-4-CF₃ O 3-349 168 t-Bu H Et H 2,6-Cl₂-4-CF₃ O 3-350 t-Bu H Et H2-Cl-6-F-4-CF₃ O 3-351 Hex H Et H 2,6-Cl₂-4-CF₃ O 3-352 Hex H Et H2-Cl-6-F-4-CF₃ O 3-353 166 c-Pr H Et H 2,6-Cl₂-4-CF₃ O 3-354 c-Pr H Et H2-Cl-6-F-4-CF₃ O 3-355 c-Hex H Et H 2,6-Cl₂-4-CF₃ O 3-356 c-Hex H Et H2-Cl-6-F-4-CF₃ O 3-357 MeOCH₂ H H H 2,6-Cl₂-4-CF₃ O 3-358 MeOCH₂ H H H2-Cl-6-F-4-CF₃ O 3-359 MeOCH₂ H Me H 2,6-Cl₂-4-CF₃ O 3-360 MeOCH₂ H Me H2-Cl-6-F-4-CF₃ O 3-361 170 MeOCH₂ H Et H 2,6-Cl₂-4-CF₃ O 3-362 MeOCH₂ HEt H 2-Cl-6-F-4-CF₃ O 3-363 CF₃ H H H 2,6-Cl₂-4-CF₃ O 3-364 CF₃ H H H2-Cl-6-F-4-CF₃ O 3-365 CF₃ H Me H 2,6-Cl₂-4-CF₃ O 3-366 CF₃ H Me H2-Cl-6-F-4-CF₃ O 3-367 172 CF₃ H Me H 2-NO₂-4-CF₃ O 3-368 CF₃ H Et H2,6-Cl₂-4-CF₃ O 3-369 CF₃ H Et H 2-Cl-6-F-4-CF₃ O 3-370 241 CF₃ H i-Pri-Pr 2-NO₂-4-CF₃ O 3-371 250 CCl₃ H Pr H 2,6-Cl₂-4-CF₃ O 3-372 249 CCl₃H i-Pr H 2,6-Cl₂-4-CF₃ O 3-373 171 EtO₂CH₂ H Et H 2,6-Cl₂-4-CF₃ O 3-374EtO₂CH₂ H Et H 2-Cl-6-F-4-CF₃ O 3-375 175 MeO₂C H Et H 2,6-Cl₂-4-CF₃ O3-373 MeO₂C H Et H 2-Cl-6-F-4-CF₃ O 3-377 3-Cl-C₆H₅ H Et H 2,6-Cl₂-4-CF₃O 3-378 3-Cl-C₆H₅ H Et H 2-Cl-6-F-4-CF₃ O 3-379 176 4-Cl-C₆H₅ H Et H2,6-Cl₂-4-CF₃ O 3-380 4-Cl-C₆H₅ H Et H 2-Cl-6-F-4-CF₃ O 3-381 4-Br-C₆H₅H Et H 2,6-Cl₂-4-CF₃ O 3-382 4-Br-C₆H₅ H Et H 2-Cl-6-F-4-CF₃ O

TABLE 4 Synthesis of 3-(substituted Pyridyloxy) pyrazole derivatives

Compound Example No. No. R¹ R² R³ R⁴ Xn Y 4-1 Me H H H 3,5-Cl₂ O 4-2 225Me H H H 3-Cl-5-CF₃ O 4-3 Me H H H 3-Cl-5-CF₃ S 4-4 Me H H H 5-CF₃ O 4-5Me H Me H 3,5-Cl₂ O 4-6 133 Me H Me H 3-Cl-5-CF₃ O 4-7 187 Me H Me H3-Cl-5-CF₃ S 4-8 Me H Me H 5-CF₃ O 4-9 Me H Me H 3,5-(NO₂)₂ O 4-10 237Me H Me Me 3-Cl-5-CF₃ O 4-11 265 Me H Me MeOCH₂ 3-Cl-5-CF₃ O 4-12 Me HMe MeOCH₂ 3-Cl-5-CF₃ O 4-13 131 Me H Et H 4-Me-6-NO₂ 0 4-14 130 Me H EtH 3-NO₂-6-MeO O 4-15 129 Me H Et H 3,5-Cl₂ O 4-16 134 Me H Et H3-Cl-5-CF₃ O 4-17 188 Me H Et H 3-Cl-5-CF₃ S 4-18 Me H Et H 5-CF₃ O 4-19Me H Et H 3,5-(NO₂)₂ O 4-20 Me H Et Me 3-Cl-5-CF₃ O 4-21 235 Me H Et Et3-Cl-5-CF₃ O 4-22 Me H Et MeOCH₂ 3-Cl-5-CF₃ O 4-23 135 Me H Pr H3-Cl-5-CF₃ O 4-24 189 Me H Pr H 3-Cl-5-CF₃ S 4-25 132 Me H i-Pr H3-Cl-5-CF₃ O 4-26 190 Me H i-Pr H 3-Cl-5-CF₃ S 4-27 236 Me H i-Pr i-Pr3-Cl-5-CF₃ O 4-28 233 Me H Bu H 3-Cl-5-CF₃ C 4-29 191 Me H Bu H3-Cl-5-CF₃ S 4-30 218 Me H s-Bu H 3-Cl-5-CF₃ O 4-31 220 Me H i-Bu H3-Cl-5-CF₃ O 4-32 136 Me H t-Bu H 3-Cl-5-CF₃ O 4-33 137 Me H Pent H3-Cl-5-CF₃ O 4-34 Me H 2-Pent H 3-Cl-5-CF₃ O 4-35 138 Me H Hex H3-Cl-5-CF₃ O 4-36 139 Me H Hep H 3-Cl-5-CF₃ O 4-37 140 Me H Oct H3-Cl-5-CF₃ O 4-38 141 Me H Dod H 3-Cl-5-CF₃ O 4-39 219 Me H c-Pr H3-Cl-5-CF₃ O 4-40 142 Me H c-Hex H 3-Cl-5-CF₃ O 4-41 197 Me H H₂C═CH H3-Cl-5-CF₃ S 4-42 143 Me H H₂C═CHCH₂ H 3-Cl-5-CF₃ O 4-43 192 Me HH₂C═CHCH₂ H 3-Cl-5-CF₃ S 4-44 Me H HC≡CCH₂ H 3-Cl-5-CF₃ O 4-45 Me HCF₃CH₂ H 3-Cl-5-CF₃ O 4-46 144 Me H 2-ClO₂H₄ H 3-Cl-5-CF₃ O 4-47 Me H2-BrC₂H₄ H 3-Cl-5-CF₃ O 4-48 Me H 2-FC₂H₄ H 3-Cl-5-CF₃ O 4-49 Me H—HOC₂H₄ H 3-Cl-5-CF₃ O 4-50 221 Me H MeO H 3-Cl-5-CF₃ O 4-51 222 Me HEtC H 3-Cl-5-CF₃ O 4-52 Me H H₂O═CHCH₂O H 3-Cl-5-CF₃ O 4-53 Me HC₆H₅CH₂O H 3-Cl-5-CF₃ O 4-54 193 Me H MeOCH₂ H 3-Cl-5-CF₃ S 4-55 194 MeH MeOCH₂CH₂ H 3-Cl-5-CF₃ S 4-56 195 Me H (CH₃)₂CH(CO₂Me)H H 3-Cl-5-CF₃ S4-57 145 Me H C₆H₅ H 3-Cl-5-CF₃ O 4-58 146 Me H 3-Cl-C₆H₄ H 3-Cl-5-CF₃ O4-59 Me H 4-Cl-C₆H₄ H 3-Cl-5-CF₃ O 4-60 Me H 2,4-Cl₂-C₆H₃ H 3-Cl-5-CF₃ O4-61 147 Me H 3,4-Cl₂-C₆H₃ H 3-Cl-5-CF₃ O 4-62 148 Me H 3-CF₃-C₆H₄ H3-Cl-5-CF₃ O 4-63 149 Me H 4-CF₃-C₆H₄ H 3-Cl-5-CF₃ O 4-64 150 Me H3-NO₂-C₆H₄ H 3-Cl-5-CF₃ O 4-65 196 Me H 4-Cl-C₆H₄CH₂ H 3-Cl-5-CF₃ S 4-66252 Me Cl Me H 3-Cl-5-CF₃ O 4-67 251 Me Cl Et H 3-Cl-5-CF₃ O 4-68 253 MeCl Pr H 3-Cl-5-CF₃ O 4-69 254 Me Cl i-Pr H 3-Cl-5-CF₃ O 4-70 255 Me ClPent H 3-Cl-5-CF₃ O 4-71 256 Me Cl Hex H 3-Cl-5-CF₃ O 4-72 257 Me Cl HepH 3-Cl-5-CF₃ O 4-73 258 Me Cl Oct H 3-Cl-5-CF₃ O 4-74 259 Me Cl Dod H3-Cl-5-CF₃ O 4-75 260 Me Cl c-Hex H 3-Cl-5-CF₃ O 4-76 Me Cl HC≡CCH₂ H3-Cl-5-CF₃ O 4-77 261 Me Cl ClC₂H₄ H 3-Cl-5-CF₃ O 4-78 263 Me Br Et H3-Cl-5-CF₃ O 4-79 Me Me H H 3-Cl-5-CF₃ O 4-80 154 Me Me Me H 3-Cl-5-CF₃O 4-81 155 Me Me Et H 3-Cl-5-CF₃ O 4-82 153 Me Me i-Pr H 3-Cl-5-CF₃ O4-83 Me Et H H 3-Cl-5-CF₃ O 4-84 158 Me Et Me H 3-Cl-5-CF₃ O 4-85 159 MeEt Et H 3-Cl-5-CF₃ O 4-86 Et H H H 3-Cl-5-CF₃ O 4-87 164 Et H Me H3-Cl-5-CF₃ O 4-88 165 Et H Et H 3-Cl-5-CF₃ O 4-89 262 Et Cl Me H3-Cl-5-CF₃ O 4-90 CF₃ H H H 3-Cl-5-CF₃ O 4-91 176 CF₃ H Me H 3-Cl-5-CF₃O 4-92 238 CF₃ H Me Me 3-Cl-S-CF₃ O 4-93 173 CF₃ H Et H 3-Cl-5-CF₃ O4-94 239 CF₃ H Et Et 3-Cl-5-CF₃ O 4-95 240 CF₃ H i-Pr i-Pr 3-Cl-5-CF₃ O

When the compound of the present invention is used as a herbicide, itcan be used as it is. It can be also used in the form of a herbicidecontaining one or more adjuvants in combination. Generally, asadjuvants, various carriers, extenders, solvents, surfactants andstabilizers are incorporated, and the compound of the present inventionis preferably formed into preparations in the form of a wettable powder,an emulsifiable concentrate, a dust, granules, a flowable agent or thelike.

The solvent as one adjuvant in the herbicide containing the compound ofthe present invention as an active ingredient is properly selected fromwater, alcohols, ketones, ethers, aliphatic and aromatic hydrocarbons,halogenated hydrocarbons, acid amides, esters or nitriles. One of thesesolvents may be used, or a mixture of two or more solvents of these maybe used.

The extender is selected from mineral powders including clays such askaolin and bentonite, talcs such as talc and pyrophyllite, oxides suchas diatomite and white carbon or plant powders such as soybean powderand CMC. Further, a surfactant may be used as a spreading agent, adispersant, an emulsifier or a penetrant. The surfactant includes, forexample, nonionic surfactants, cationic surfactants and amphotericsurfactants. These surfactants are used alone or as a mixture of atleast two members of these depending upon an end in use.

The method of use of a herbicide containing the compound of the presentinvention as an active ingredient includes soil treatment, water surfacetreatment, foliar treatment, and the herbicide can produce an excellenteffect when applied before and during germination.

Further, the herbicide containing the compound of the present inventionas an active ingredient may contain other active components such asother herbicide, an insecticide, a fungicide, a plant growth regulator,etc., in combination, or may be used in combination with these.

The present invention will be explained further in detail with referenceto Preparation Examples of herbicides containing the compound of thepresent invention as an active ingredient and Examples of testingherbicides for herbicidal efficacy. In addition, “part” stands for “partby weight”.

Preparation Example 1 Emulsifiable Concentrate

20 Parts of a compound of the present invention, 35 parts of xylene, 40parts of cyclohexanone and 5 parts of Sorpol 900A (supplied by TohoChemical Co., Ltd.) were homogeneously mixed, to give an emulsifiableconcentrate.

Preparation Example 2 Wettable Powder

50 Parts of a compound of the present invention, 25 parts of diatomite,22 parts of clay and 3 parts of Lunox 1000C (supplied by Toho ChemicalCo., Ltd.) were homogenously mixed and pulverized, to give a wettablepowder.

Preparation Example 3 Granules

A mixture containing 5 parts of a compound of the present invention, 35parts of bentonite, 55 parts of talc, 5 parts of sodium ligninsulfonatewas homogenously mixed and pulverized, and then water was added. Themixture was kneaded and granulated with an extrusion granulator, and thegranulated product was dried and particle-size-adjusted, to givegranules.

The compound of the present invention was tested for herbicidal efficacyaccording to those methods shown in the following Test Examples withregard to preparations prepared according to the above-shown methods.The herbicidal efficacy thereof on test weeds and their phytotoxicity totest crops were evaluated on the basis of five ratings in which 1 showsno influence and 5 shows complete die.

Test Example 1 Herbicidal Efficacy Test by Pre-Emergence Treatment UnderSubmergence Condition

A 1/10,000-are pot was filled with paddy field soil, and, after plowing,seeds of Echinochloa oryzicola, Cyperus difformis, Monochoria vaginalis,Scirpus juncoides, Eleocharis acicularis and other annual broadleafweeds such as Lindernia procumbens, Rotala indica and Elatine triandrawere sown. Rice (oryza sativa) seedlings (cultiver “Koshihikari”) at a2.5-leaf stage were transplanted and kept under a submergence condition.After one day, the wettable powder or emulsifiable concentrate of thecompound of the present invention, prepared according to PreparationExample, was diluted and dropped on a water surface at a predetermineddose. On the 15^(th) day after the treatment, the herbicidal efficacy onthe test weeds and the injury to the rice were investigated on the basisof the ratings of 1 to 5, and Table 5 shows the results.

TABLE 5 Herbicidal efficacy test by pre-emergence treatment undersubmergence condition Comp'd Dose Herbicidal efficacy Injury No. kg/haEo Cd Blw Mv Sj Ea Os 3-3  1 5 5 5 5 5 5 1.5 0.5 5 5 5 5 5 5 1.5 3-14 15 5 5 5 5 5 2.5 0.5 5 5 5 5 5 5 2.3 3-15 1 5 5 5 5 5 5 1.5 0.5 5 5 5 5 55 1.3 3-44 1 5 5 5 5 5 5 3.5 0.5 5 5 5 5 5 5 2.5 3-45 1 5 5 5 5 5 5 1.70.5 5 5 5 5 4 5 1.5 3-74 1 5 5 5 5 5 5 1.8 0.5 5 5 5 5 5 5 1.8 3-89 1 55 5 5 5 5 1.5 0.5 5 5 5 5 5 5 1.3  3-130 1 5 5 5 5 5 5 1.8 0.5 5 5 5 5 55 1.5  3-143 1 5 5 5 5 5 5 1.5 0.5 5 5 5 5 4 5 1.3  3-146 1 5 5 5 5 5 51 0.5 5 5 5 5 5 5 1  3-158 1 5 5 5 5 5 5 2 0.5 5 5 5 5 5 5 1.5  3-169 15 5 5 5 4.2 5 1 0.5 5 5 5 5 4 5 1  3-183 1 5 5 5 5 5 5 2 0.5 5 5 5 5 5 52  3-249 1 5 5 5 5 5 5 1.5 0.5 5 5 5 5 5 5 1.2  3-253 1 5 5 5 5 5 5 1.60.5 5 5 5 5 5 5 1.4  3-330 1 5 5 5 5 5 5 1.5 0.5 5 5 5 5 5 5 1.2 4-6  15 5 5 5 5 5 1.4 0.5 4.8 5 5 5 4.6 5 1.2 4-16 1 5 5 5 5 5 5 2.5 0.5 5 5 55 4.8 5 2 4-17 1 5 5 5 5 4.8 5 1.8 0.5 5 5 4.8 5 4.5 5 1.5 4-23 1 5 5 55 5 5 1.3 0.5 5 5 4.8 5 4.9 5 1.1 Eo: Echinochloa oryzicola, Cd: Cyperusdifformis, Blw: anuual broadleaf weeds, Mv: Monochoria vaginalis, Sj:Scirpus juncoides, Ea: Eleocharis acicularis, Os: Oryza sativa

Test Example 2 Herbicidal Efficacy Test by Soil Treatment BeforeGermination Under Upland Field Condition

A vat having an area of 5×10 cm² and a depth of 5 cm was filled withupland field soil, and seeds of Chenopodium album, Echinochloacrus-galli, Amaranthus viridis, Digitaria ciliaris and sweet corn (Zeamays) were sown thereon and covered with soil by a depth of 0.5 cm. Nextday, the wettable powder or emulsifiable concentrate of the compound ofthe present invention, prepared according to Preparation Example, wasdiluted and sprayed uniformly onto the covering soil at a predetermineddose. On the 21st day after the treatment, the herbicidal efficacy onthe test weeds and the injury to the corn were investigated on the basisof the ratings of 1 to 5, and Table 6 shows the results.

TABLE 6 Herbicidal efficacy test by soil treatment before germinationunder upland field condition Comp'd Dose Herbicidal activity Injury No.kg/ha Ca Ec Av Dc Zm 3-3  1 5 3.5 5 4.5 1.5 3-14  1 5 4.9 5 5 — 3-44  15 5 5 5 3 3-45  1 5 5 5 5 2 3-74  1 5 4.9 5 5 1 3-183 1 5 3 5 4 1 3-2491 5 4.5 5 5 1.2 3-253 1 5 4 5 5 1.5 3-330 1 5 3.5 5 5 1.5 Ca:Chenopodium album, Ec: Echinochloa crus-galli, Av: Amaranthus viridis,Dc: Digitaria ciliaris, Zm: Zea mays.

Test Example 3 Herbicidal Efficacy Test by Foliar Treatment AfterGermination Under Upland Field Condition

A vat having an area of 5×10 cm² and a depth of 5 cm was filled withupland field soil, and seeds of Chenopodium album, Echinochloacrus-galli, Amaranthus viridis and Abutilon theophrasti were sownthereon and covered with soil by a depth of 0.5 cm. Water was sprayed asrequired to grow them for 14 days. The wettable powder or emulsifiableconcentrate of the compound of the present invention, prepared accordingto Preparation Example, was diluted and sprayed uniformly to shoot ofthe plants at a dose of 1,000 liters/ha. On the 14^(th) day after thetreatment, the herbicidal efficacy on the test weeds were investigatedon the basis of the ratings of 1 to 5, and Table 7 shows the results.

TABLE 7 Herbicidal efficacy test by foliar treatment after germinationunder upland field condition Comp'd Dose Herbicidal activity No. kg/haCa Ec Av Dc 3-3  1 5 4.5 5 5 3-14 1 5 5 5 5 3-15 1 5 5 5 5 3-44 1 5 5 55 3-45 1 5 5 5 5 3-67 1 5 4.9 5 5 3-74 1 5 4.9 5 5 3-82 1 5 3.8 5 5 3-891 5 5 5 5  3-130 1 5 5 5 5  3-158 1 5 5 5 5  3-183 1 5 5 5 5  3-249 1 55 5 5  3-253 1 5 5 5 5  3-330 1 5 5 5 5 4-30 1 5 5 5 5 Ca: Chenopodiumalbum, Ec: Echinochloa crus-galli, Av: Amaranthus viridis, Dc: Digitariaciliaris.

INDUSTRIAL UTILITY

The pyrazole derivative of the present invention exhibits excellentherbicidal activity at a low dosage without causing phytotoxicity oncrops and has utility as a herbicide.

1. A pyrazole of formula (I),

wherein: R¹ is a hydrogen atom; an alkyl group having 1 to 6 carbonatoms which is unsubstituted or substituted by halogen, alkoxy having 1to 6 carbon atoms or alkyloxycarbonyl having 1 to 6 carbon atoms; acycloalkyl group having 3 to 8 carbon atoms; an alkyloxycarbonyl grouphaving 1 to 6 carbon atoms; or a phenyl group which is unsubstituted orsubstituted by alkyl having 1 to 12 carbon atoms or halogen; R² is ahydrogen atom; R³ is a hydrogen atom; an alkyl group having 1 to 12carbon atoms which is unsubstituted or substituted by halogen, hydroxyl,formyl, alkoxy having 1 to 6 carbon atoms, alkyloxycarbonyl having 1 to6 carbon atoms, or heterocyclic ring selected from the group consistingof 2-furyl, 2-tetrahydrofuryl, 2-thienyl, 1,3-dioxolan-2-yl,1,3-dioxinan-2-yl, morpholino, and 2-pyridyl; a cycloalkyl group having3 to 8 carbon atoms; an aralkyl group having 7 to 11 carbon atoms; analkenyl group having 3 to 6 carbon atoms; an alkynyl group having 3 to 6carbon atoms; a phenyl group which is unsubstituted or substituted byhalogen, alkyl having 1 to 12 carbon atoms, trifluoromethyl, or nitro;an alkyloxy group having 1 to 6 carbon atoms; a cycloalkyloxy grouphaving 3 to 8 carbon atoms; an aralkyloxy group having 7 to 11 carbonatoms; an alkenyloxy group having 3 to 6 carbon atoms; an alkynyloxygroup having 3 to 6 carbon atom; or a phenyloxy group; R⁴ is a hydrogenatom; R⁵ is a 4-trifluoromethyl phenyl group which is unsubstituted orsubstituted by a halogen atom or nitro; and Y is an oxygen atom or asulfur atom.
 2. A herbicide containing, as an active ingredient, apyrazole of claim
 1. 3. The pyrazole of claim 1, wherein R¹ is ahydrogen atom, or an alkyl group having 1 to 6 carbon atoms which isunsubstituted or substituted by halogen, alkoxy having 1 to 6 carbonatoms, or alkyloxycarbonyl having 1 to 6 carbon atoms.
 4. The pyrazoleof claim 1, wherein R³ is a hydrogen atom; an alkyl group having 1 to 12carbon atoms which is unsubstituted or substituted by halogen, hydroxyl,formyl, alkoxy having 1 to 6 carbon atoms, alkyloxycarbonyl having 1 to6 carbon atoms, or a heterocyclic ring selected from the groupconsisting of 2-furyl, 2-tetrahydrofuryl, 2-thienyl, 1,3-dioxolan-2-yl,1,3-dioxinan-2-yl, morpholino, and 2-pyridyl; a cycloalkyl group having3 to 8 carbon atoms; an aralkyl group having 7 to 11 carbon atomsselected from the group consisting of benzyl, 1-phenylethyl and2-phenylethyl; an alkenyl group having 3 to 6 carbon atoms; an alkynylgroup having 3 to 6 carbon atoms; a phenyl group which is unsubstitutedor substituted by halogen, alkyl having 1 to 12 carbon atoms,trifluoromethyl or nitro; an alkyloxy group having 1 to 6 carbon atoms;or a cycloalkyloxy group having 3 to 8 carbon atoms.
 5. The pyrazole ofclaim 4, wherein R³ is a hydrogen atom, or an alkyl group having 1 to 12carbon atoms which is unsubstituted or substituted by halogen, hydroxyl,formyl, alkoxy having 1 to 6 carbon atoms, alkyloxycarbonyl having 1 to6 carbon atoms, or a heterocyclic ring selected from the groupconsisting of 2-furyl, 2-tetrahydrofuryl, 2-thienyl, 1,3-dioxolan-2-yl,1,3-dioxinan-2-yl, morpholino, and 2-pyridyl.
 6. The pyrazole of claim1, wherein Y is an oxygen atom.
 7. The pyrazole of claim 1, having theformula:

wherein X¹ and X² are each independently a halogen.
 8. The pyrazole ofclaim 7, wherein X¹ and X² are each independently chlorine or fluorine.